Open Access

Functional mechanisms of circular RNA‑encoded peptides and future research strategies and directions in nasopharyngeal carcinoma (Review)

  • Authors:
    • Weihua Xu
    • Zhichao Ma
    • Wei Gong
    • Shengmiao Fu
    • Xinping Chen
  • View Affiliations

  • Published online on: August 18, 2025     https://doi.org/10.3892/ijo.2025.5788
  • Article Number: 82
  • Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy closely associated with Epstein‑Barr virus (EBV) infection. Although patients with early‑stage NPC can achieve a high cure rate through radiotherapy, recurrence and distant metastasis remain the primary causes of treatment failure in patients with advanced‑stage NPC. Circular RNA (circRNA) is a class of covalently closed non‑coding RNAs involved in multiple aspects of tumor biology. Recent evidence has shown that certain circRNAs can encode functional peptides, which participate in the regulation of tumor‑related signaling pathways. In NPC, circRNAs have been implicated in the modulation of signaling pathways, including NF‑κB and JAK/STAT, both of which are activated in the EBV‑infected microenvironment. Furthermore, frequently mutated genes in NPC, such as TNF receptor‑associated factor 3 and cylindromatosis lysine 63 deubiquitinase, are known regulators of the NF‑κB pathway, suggesting a potential link between genetic alterations and circRNA‑related mechanisms. This article systematically reviews the biological mechanisms of circRNA‑encoded peptides, summarizes the expression and function of circRNA in NPC and focuses on discussing the potential roles of circRNA‑encoded peptides in tumor microenvironment regulation, immune escape and clinical application prospects. By integrating existing research results, this article aims to provide a new perspective and theoretical basis for the in‑depth exploration of circRNA‑encoded peptides in the field of NPC.

Introduction

Nasopharyngeal carcinoma (NPC) is an epithelial tumor prevalent in Southern China and Southeast Asia (1,2). NPC is strongly associated with Epstein-Barr virus (EBV) infection, which plays a critical role in the development and progression of NPC (3,4). Although patients with early-stage NPC can achieve high cure rates through radiotherapy, most are diagnosed at advanced local or metastatic stages, facing high risks of recurrence and metastasis (5,6).

Circular RNA (circRNA) is a class of non-coding RNA characterized by a covalently closed-loop structure, which confers enhanced stability and abundance, thereby implicating circRNAs as important regulators in cancer development (7,8). Their biological relevance in cancer is under active investigation.

In NPC, accumulating evidence has demonstrated that circRNAs play essential roles in tumor progression. For instance, circPVT1 promotes NPC metastasis through a β-transducin repeat-containing protein (β-TrCP)/cellular myelocytomatosis oncogene/Serine/arginine-rich splicing factor 1 feedback loop, while circHIPK2 promotes NPC cell proliferation by downregulating its parental gene HIPK2 (9-11). Furthermore, circRNAs have been shown to participate in chemotherapy-induced senescence reprogramming, further implicating them in treatment resistance and metastasis (9,10).

Beyond traditional non-coding functions, certain circRNAs can encode peptides with distinct biological functions, expanding the landscape of their regulatory capacity. Although research on circRNA-encoded peptides in NPC is currently lacking, such peptides have been functionally validated in other cancers. For instance, circMTHFD2L encodes CM-248aa, which inhibits gastric cancer progression via the SET-PP2A axis, and circCOL6A3_030 produces a polypeptide that promotes gastric cancer metastasis (12,13). Similarly, circEIF6 encodes EIF6-224aa to enhance triple-negative breast cancer progression and circINSIG1 encodes a peptide that modulates cholesterol metabolism in colorectal cancer (14,15).

These findings suggest that circRNA-encoded peptides may represent a novel regulatory layer with potential relevance in NPC, particularly given the established role of circRNA in this malignancy. However, direct studies in NPC are still absent and further investigation is needed to elucidate their functions in this context.

Given the functional relevance of circRNA in NPC and the role of their encoded peptides in cancer biology, it is important to clarify whether similar mechanisms exist in NPC. This article focuses on the current understanding of the biology of cyclic ribonucleic acid in NPC, the mechanistic basis of circRNA-encoded peptides, and their potential roles in tumor signaling and microenvironment regulation, providing a foundation for future research in this underexplored field.

Biological mechanisms of peptides encoded by circRNA

Structure and functional diversity of circRNA

The circular structure of circRNA is formed through back-splicing of precursor mRNA, which is a process of connecting downstream splicing donors with upstream splice acceptors (16). Unlike linear RNA, circRNAs lack a 5′cap and a 3′polyadenylation [poly(A)] tail, which contributes to their enhanced stability and resistance to exonuclease-mediated degradation compared to their linear counterparts (17). Additionally, circRNAs display high sequence conservation and tissue- or developmental stage-specific expression patterns (18). These unique structural properties confer exceptional long-term cellular stability to circRNAs, enabling their function as efficient microRNA (miRNA) sponges, scaffolds for protein interactions and modulators of gene transcription and splicing (19,20). Recent studies have demonstrated the pivotal role of circRNA in various diseases, particularly in cancer, where it orchestrates critical biological processes such as tumor cell proliferation, migration and invasion (19,21). Dysregulated expression of circRNA in colorectal cancer, gliomas and thyroid cancer has been extensively documented, underscoring their potential as reliable biomarkers for early diagnosis and prognosis evaluation (16,20,22). Additionally, leveraging the unique mechanisms of circRNA, such as their ability to act as miRNA sponges, offers novel therapeutic strategies to enhance the precision and efficacy of targeted cancer therapies (23,24).

In summary, research on circRNA has revealed its significant role in cellular biology and disease progression, particularly in cancer. With a deeper understanding of its biological functions and mechanisms, circRNA holds promise as a versatile molecular biomarker in cancer diagnosis, treatment and prognosis evaluation, paving the way for more personalized and effective therapeutic interventions.

Translation mechanisms of circRNA

The translation of circRNA relies on cap-independent mechanisms, including internal ribosome entry sites (IRES) and N6-methyladenosine (m6A)-mediated IRES (MIRES), which collectively enhance translational efficiency and specificity (25,26). IRES elements allow translation to occur without the traditional 5′cap structure, while m6A modifications enhance the efficiency and selectivity of this cap-independent translation (27). IRES is a special RNA sequence that can directly bind ribosomes and initiate translation, bypassing the traditional cap-dependent initiation mechanisms (28,29). m6A, a widespread RNA modification, plays a pivotal role in the translational regulation of circRNA by modulating the recruitment of translation initiation factors (30). Studies have shown that m6A-modified circRNA can recruit the translation initiation complex directly via m6A reader proteins like YTH N6-methyladenosine RNA-binding protein family activators, facilitating translation through MIRES, providing an alternative to the traditional cap-dependent translation initiation mechanism (31). Furthermore, specific features, such as open reading frames (ORFs) and structural motifs, enhance the translational potential of circRNAs, allowing a subset to encode functional proteins or peptides (32,33). In certain cases, a rolling translation mechanism enables continuous translation from an ORF even without IRES or MIRES (26,34). The translation mechanism of circRNA is shown in Fig. 1.

Research into circRNA translation not only deepens the current understanding of disease mechanisms but also uncovers new molecular targets for disease diagnosis and therapy (35,36). For instance, circRNA MTCL1 promotes the progression of advanced laryngeal squamous cell carcinoma by inhibiting C1QBP ubiquitin degradation and mediating β-catenin activation (37). Furthermore, circRNA-derived peptides may modulate cellular functions and signaling pathways, indicating their emerging importance in physiological and pathological processes (38). Collectively, current findings suggest that circRNA-encoded peptides represent a promising area of research with potential implications for disease diagnosis and therapeutic development (39,40).

Expression and function of circRNA in NPC

Expression profile analysis of circRNA in NPC

Recent studies analyzing circRNA expression profiles in NPC have revealed their critical potential to regulate tumor progression, offering novel insights into diagnostic and therapeutic strategies (41). Recent studies indicate that circRNA can regulate NPC cell proliferation, migration and invasion by modulating multiple signaling pathways, such as the Wnt/β-catenin pathway (42) and competing endogenous RNA (ceRNA) networks (43).

Studying the expression profiles of circRNA not only helps to reveal their mechanism of action in the development of NPC but may also provide important information for early diagnosis, prognosis assessment and the development of new therapeutic targets. For instance, analysis of the circRNA-miRNA-target gene network revealed that hsa_circ_0002375 (circKITLG) may play a pivotal role in the potential mechanism of NPC by acting as a sponge for miR-3198 and disrupting its downstream targets, and experimental silencing of circKITLG inhibits the proliferation, migration and invasion of NPC cells in vitro (41). In addition, researchers have investigated the spectrum of differentially expressed circRNA in NPC and found that hsa_circ_0007637 may be a biomarker for NPC and play a role in its development (44). It has been shown that hsa_circ_0044569 (circCOL1A1) exerts its oncogenic role in NPC by precisely regulating the miR-370-5p/PTMA signaling axis, thereby promoting tumor growth and progression (45).

Although studies have revealed diverse functions of circRNA in NPC, this field still faces significant challenges and limitations. For instance, a thorough understanding of the complete expression profile of circRNA is still lacking and the connection between circRNA and the pathophysiological characteristics of cancer needs to be further clarified (46). While numerous circRNAs have been identified, the specific roles of many remain to be investigated (44).

In summary, profiling circRNA in NPC offers valuable insight into disease-related molecular changes and may contribute to improved diagnostic and therapeutic approaches. Continued research may help clarify the biological functions of circRNA and facilitate their clinical application.

Regulatory roles and functions of circRNA in NPC

In NPC, circRNAs interact with miRNAs to form complex ceRNA networks, thereby precisely regulating the expression of downstream genes and driving the progression of NPC (47). A study has found that circFIP1L1 enhances NPC cell radiosensitivity by directly inhibiting the expression of miR-1253, highlighting its potential role in modulating NPC response to radiation therapy (48). Furthermore, circCTDP1 interacts with miR-320b to further regulate the expression of HOXA10 and TGFβ2, promoting NPC cell proliferation and migration, underscoring the complex regulatory role of circRNAs in NPC progression (49). Research indicates that circNRIP1 enhances NPC cell resistance to 5-Fu and cisplatin by modulating the miR-515-5p/IL-25 axis, suggesting its potential as a new target for reversing NPC chemotherapy resistance (50). Similarly, a study by Yin et al (51) showed that circ-0046263 promotes NPC progression by acting as a sponge for miR-133a-5p and upregulating IGFBP3 expression, thereby driving tumor growth. Additionally, circ-ABCB10 has been found to promote NPC cell proliferation and metastasis by upregulating ROCK1 (52), further highlighting the significant role of circRNA in tumor metastasis.

The complex regulatory networks involving circRNA in NPC are being progressively elucidated. Through bioinformatics analysis, researchers have identified key genes associated with NPC and predicted the potential of circRNA to regulate these genes via ceRNA mechanisms (53). Furthermore, Chen et al (53) discovered through bioinformatics analysis that numerous circRNAs may regulate the expression of the key gene FN1, thereby affecting NPC progression. Likewise, Li and Wang (54) reported that hsa_circ_0081534 promotes NPC cell proliferation and invasion by regulating the miR-508-5p/FN1 axis.

In NPC, there are multi-level interactions between circRNA and EBV factors, forming an important mechanistic network for regulating tumor progression. EBV-encoded circBART2.2, a virus-derived circRNA, can upregulate PD-L1 expression, weaken T-cell immune function and help tumors achieve immune escape (55). In addition, EBV indirectly affects the splicing and expression patterns of host circRNA by reshaping the host's epigenetic landscape and enhancing inflammation-related gene expression, providing a basis for NPC molecular typing and treatment response differences (56). EBV-associated glycoproteins can alter the membrane structure and extracellular vesicle secretion of tumor cells, which may affect the transport and function of circRNA between cells (57). EBV also inhibits natural killer cell function by upregulating B7-H3, coupled with circRNA-mediated immune regulation, exacerbating the tumor immune suppressive microenvironment (58). Meanwhile, studies have confirmed that EBV induces GPX4 expression and enhances cellular drug resistance, which may involve the cross action of circRNA regulation of lipid metabolism and antiapoptotic pathways (59). Metabolomics and animal model studies further indicate that EBV can promote sustained activation of circRNA-related pathways and drive malignant progression of NPC by activating glycolysis and lipid metabolism pathways (60,61). In addition, the EGFR signaling pathway is activated in EBV infection and interacts with multiple oncogenic pathways regulated by circRNA, amplifying oncogenic signals (62). It is worth noting that EBV forms systematic reprogramming with host ceRNA networks (including circRNA) through its protein products, and cooperatively promotes NPC generation at multiple levels of chromatin, epigenetics and post-transcriptional regulation (63,64). Furthermore, host genetic variations may regulate responses to different EBV subtypes and the interaction of these genetic virus circRNA forms a complex NPC risk regulatory network (65).

In summary, circRNA not only serves as a regulatory factor within host cells but may also play an important role as a 'signaling node' in virus host interactions, providing a new research perspective for understanding the virus-driven mechanisms of NPC and laying a theoretical foundation for developing virus-related molecular targeting strategies.

Molecular mechanisms of circRNA-encoded peptides in cancer

Role of circRNA-encoded peptides in cancer

CircRNA-encoded peptides have been experimentally validated as regulators of multiple oncogenic pathways in various cancers (66,67). For instance, AXIN1-295aa derived from circAXIN1 activates Wnt/β-catenin signaling by disrupting the adenomatous polyposis coli (APC)-containing destruction complex, promoting gastric cancer progression (68). Similarly, circPDHK1 encodes PDHK1-241aa, which binds PPP1CA and prevents AKT dephosphorylation, thereby promoting AKT/mTOR signaling activation in renal cancer (69). Other examples include TRIM1-269aa from circTRIM1, which enhances PI3K/AKT/mTOR signaling and chemoresistance in breast cancer (70), and MAPK1-109aa from circMAPK1, which inhibits MAPK1 phosphorylation and suppresses gastric tumor cell growth (71).

Although similar peptides have not yet been identified in NPC, circRNA has been shown to play functional roles in this cancer type through non-coding mechanisms. For instance, hsa_circ_0081534 promotes proliferation and invasion in NPC via the miR-508-5p/FN1 axis (54).

These parallels suggest that circRNA-encoded peptides may represent an uncharted but relevant layer of regulation in NPC. Further investigation using proteomics and functional models such as NPC organoids will be essential to determine their presence and roles in this disease context.

CircRNA-encoded polypeptides regulate multiple signaling pathways

CircRNA, as a type of non-coding RNA, plays a crucial role in the initiation and progression of various cancers. CircRNA can directly activate the Wnt/β-catenin signaling pathway by encoding polypeptides. For instance, the AXIN1-295aa polypeptide encoded by circAXIN1 disrupts the Wnt signaling pathway's destruction complex' by competing with the APC gene product, thereby releasing β-catenin into the nucleus and activating the expression of downstream genes, which promotes gastric cancer initiation and progression (68). Studies have shown that circRNA can modulate tumor progression through specific interactions with the PI3K/AKT/mTOR signaling pathway. For instance, the PDHK1-241aa polypeptide encoded by circPDHK1 interacts with PPP1CA, inhibiting AKT dephosphorylation, which subsequently activates the AKT-mTOR signaling pathway and promotes renal cancer progression (69). In addition, the TRIM1-269aa polypeptide encoded by circTRIM1 enhances the interaction between MARCKS and calmodulin and activates the PI3K/AKT/mTOR pathway in triple-negative breast cancer, promoting chemoresistance and metastasis (70). Research also indicates that the SEMA4B-211aa polypeptide encoded by circSEMA4B modulates the PI3K/AKT signaling pathway by inhibiting AKT phosphorylation, thereby suppressing breast cancer progression (72). CircRNA can further modulate the MAPK signaling pathway through various mechanisms. For instance, the MAPK1-109aa polypeptide encoded by circMAPK1 inhibits MAPK1 phosphorylation, blocking its activation, and subsequently suppressing the proliferation and invasion of gastric cancer cells (71).

A study revealed that the SMO-193aa polypeptide encoded by circ-SMO interacts with SMO in glioblastoma, enhancing cholesterol modification of SMO and relieving SMO receptor inhibition, thereby promoting Hedgehog signaling pathway activation (73). Additionally, Song et al (74) identified the critical function of the CAPG-171aa polypeptide encoded by circCAPG in triple-negative breast cancer, which activates the MEKK2-MEK1/2-ERK1/2 pathway by disrupting the interaction between STK38 and SMURF1, thus promoting tumor growth. In fish, the MORC3-84aa polypeptide encoded by circMORC3 interacts with TRIF, facilitating its autophagic degradation, and inhibits TRIF-mediated IRF3 and NF-κB signaling pathways, thus acting as a negative regulator of the antiviral immune response (75).

Studies have suggested that circRNA-encoded peptides may potentially participate in the regulation of key oncogenic signaling pathways in NPC, particularly NF-κB and JAK/STAT, both of which are closely associated with immune modulation and viral pathogenesis. The NF-κB pathway is frequently activated in NPC due to factors such as cancer-associated fibroblasts, inflammatory signals and regulatory proteins, supporting tumor survival and metastasis (76-79). In parallel, the JAK/STAT pathway has been linked to lymph node metastasis and poor prognosis in NPC (80,81). Notably, hsa_circ_0013561 was shown to promote NPC progression via the JAK2/STAT3 axis, implicating circRNA in the activation of this pathway (81). Although direct evidence remains limited, these findings raise the possibility that circRNA-derived peptides may act as functional modulators within these signaling cascades.

Genomic profiling has revealed that NPC frequently harbors mutations in negative regulators of NF-κB signaling, such as TRAF3 (TNF receptor-associated factor 3) and CYLD (cylindromatosis lysine 63 deubiquitinase), whose loss may amplify the impact of NF-κB-related oncogenic pathways (82-85). CYLD not only represses NF-κB but also influences post-translational modification and viral replication, suggesting that its dysfunction may modulate circRNA-mediated or circRNA-derived peptide effects at multiple levels (85,86). Furthermore, EBV infection has been shown to reshape chromatin accessibility and enhancer usage, further activating NF-κB signaling in NPC, a process that may converge with circRNA-mediated regulation (87). The potential role of circRNA-encoded peptides in NPC is shown in Fig. 2

To validate these hypotheses, recent studies have highlighted the utility of NPC organoid models and proteomic platforms, which offer powerful experimental systems to dissect the function of circRNA-encoded peptides and their interaction with key oncogenic pathways in a physiologically relevant context (78,88). Altogether, these studies jointly reveal the value of NPC pathogenesis and potential therapeutic targets.

These findings suggest that circRNA-encoded peptides may influence inflammatory and oncogenic signaling pathways, including NF-κB, which is highly relevant to NPC pathogenesis. Further mechanistic studies using NPC-specific systems, such as patient-derived organoids, will be essential to confirm these associations.

A summary of circRNA-encoded polypeptides regulating multiple signaling pathways is presented in Table I. Overall, circRNA-encoded polypeptides represent an emerging layer of molecular regulation in cancer and inflammatory diseases, with potential implications for therapeutic development.

Table I

CircRNA-encoded peptides regulate multiple signaling pathways.

Table I

CircRNA-encoded peptides regulate multiple signaling pathways.

CircRNAsEncoded peptideSignaling pathwaysAssociated disease(Refs.)
CircAXIN1AXIN1-295aaWnt/β-catenin signaling pathwayPromotes the occurrence and progression of gastric cancer(68)
CircPDHK1PDHK1-241aaPI3K/AKT/mTOR signaling pathwayPromotes the progression of renal cancer(69)
CircTRIM1TRIM1-269aaPI3K/AKT/mTOR signaling pathwayPromotes chemotherapy resistance and metastasis in triple-negative breast cancer(70)
CircSEMA4BSEMA4B-211aaPI3K/AKT signaling pathwayInhibits the progression of breast cancer(72)
CircMAPK1MAPK1-109aaMAPK signaling pathwayInhibits proliferation and invasion of gastric cancer cells(71)
Circ-SMOSMO-193aaHedgehog signaling pathwayPromotes the development of gliomatosis(73)
CircCAPGCAPG-171aaMEKK2-MEK1/2-ERK1/2 signaling pathwayPromotes tumor growth in triple-negative breast cancer(74)
CircMORC3MORC3-84aaTRIF-mediated IRF3 and NF-κB signaling pathwaysInhibitory regulation of viral immune responses(75)

[i] circRNA, circular RNA. AXIN1, axis inhibitor 1; PDHK1, pyruvate dehydrogenase kinase isoform 1; TRIM1, tripartite motif containing 1; SEMA4B, semaphorin 4B; MAPK1, mitogen-activated protein kinase 1; SMO, smoothened frizzled class receptor; CAPG, capping actin protein, gelsolin like; MORC3, MORC family CW-type zinc finger 3; Wnt, wingless-type MMTV integration site family; PI3K, phosphoinositide 3-kinase; AKT, protein kinase B; mTOR, mechanistic target of rapamycin; MAPK, mitogen-activated protein kinase; ERK1/2, extracellular signal-regulated kinases 1 and 2; MEK1/2, MAPK kinase 1/2; IRF3, interferon regulatory factor 3; NF-κB, nuclear factor κ-light-chain-enhancer of activated B cells.

Interaction between circRNA and encoded polypeptides with the tumor microenvironment (TME)

Role of circRNA in the TME

CircRNAs influence the TME through their encoded peptides, modulating tumor growth, immune evasion and stromal interactions. First, the interaction between circRNAs and tumor-associated macrophages (TAMs) is particularly significant. For instance, circSMARCC1 enhances the interaction between prostate cancer cells and TAMs through the miR-1322/CCL20/CCR6 signaling axis, promoting M2 polarization of TAMs, which accelerates tumor progression (89). Furthermore, hsa_circ_0009092 suppresses colorectal cancer proliferation and TAM recruitment by sponging miR-665 and regulating NLK expression, thereby inhibiting the Wnt/β-catenin signaling pathway (90). Second, circRNAs can modulate immune evasion within the TME. For instance, hsa_circ_0136666 modulates PD-L1 phosphorylation through the miR-375/PRKDC axis, impairing T cell-mediated immunity and facilitating immune evasion in gastric cancer (91). Similarly, circNEIL3 stabilizes the IGF2BP3 protein, promoting the immunosuppressive polarization of macrophages, which in turn accelerates glioma progression (92). EBV-encoded circRNA circBART2.2 interacts with RIG-I, activating transcription factors IRF3 and NF-κB, which promotes PD-L1 expression and inhibits T-cell function, thus facilitating immune evasion in NPC (55).

Research has shown that circRNAs can mediate information exchange between cancer cells and immune cells, fibroblasts and other components of the TME via exosomes, thus regulating key aspects of tumor proliferation, metabolism, immune escape and drug resistance (93). Similarly, cSERPINE2 in breast cancer enhances the secretion of IL-6 by TAMs, promoting cancer cell proliferation and infiltration, which exacerbates tumor progression through a positive feedback loop (94). Another critical function of circRNAs is their modulation of tumor angiogenesis, stromal remodeling and immune suppression. For instance, in esophageal squamous cell carcinoma, circRNAs enhance tumor invasiveness by modulating angiogenesis and epithelial-mesenchymal transition within the TME (95). Additionally, circRNA ZNF609 promotes angiogenesis in NPC via the miR-145/STMN1 axis, driving tumor cell proliferation and migration (96). Meanwhile, circRNA ZNF609 enhances NPC growth and metastasis by sponging miR-150-5p and upregulating Sp1 expression (97). In summary, circRNA appear to contribute to multiple aspects of TME regulation, offering potential insights into tumor biology and therapeutic targeting.

Role of circRNA-encoded peptides in the TME

CircRNA-derived peptides have been found to affect signaling pathways relevant to the TME in various tumor types. Studies have shown that the peptide C-HGF encoded by circHGF activates the c-MET signaling pathway, promoting glioblastoma growth (98). Additionally, the SEMA4B-211aa protein encoded by circSEMA4B inhibits the progression of breast cancer. Its mechanism involves binding to p85, inhibiting AKT phosphorylation, thereby regulating the PI3K/AKT signaling pathway (72). In colorectal cancer, the circMAPK14-175aa peptide encoded by circMAPK14 competes with MKK6, inhibiting cancer progression and metastasis (99). Zhang et al (100) found that the 198-aa peptide encoded by hsa_circ_0006401 promotes colorectal cancer proliferation and metastasis by stabilizing mRNA of its host gene COL6A3. Furthermore, the circPPP1R12A-73aa peptide encoded by circPPP1R12A activates the Hippo-YAP signaling pathway, promoting the growth and metastasis of colon cancer (101).

Research on chronic obstructive pulmonary disease has revealed that the circ-0008833-57aa peptide encoded by has-circ-0008833 induces apoptosis in bronchial epithelial cells, promoting the progression of chronic obstructive pulmonary disease (102). Li et al (103) found that the CORO1C-47aa peptide encoded by circ-0000437 inhibits angiogenesis, suppressing the progression of endometrial cancer. In addition, the β-TrCP-343aa peptide encoded by circ-β-TrCP competes with NRF2, blocking SCF β-TrCP-mediated proteasomal degradation of NRF2, thereby upregulating antioxidant genes and conferring resistance to trastuzumab (104). These findings collectively indicate that circRNA-derived peptides can modulate immune responses, angiogenesis, metabolism and drug sensitivity within the TME. Continued research is needed to further define their mechanistic roles and therapeutic relevance.

Prospects for the clinical application of circRNA-encoded peptides

Potential of circRNA-encoded peptides as diagnostic and prognostic biomarkers

Peptides are molecular chains formed by connecting two or more amino acids through peptide bonds. Each peptide bond is formed through the dehydration condensation reaction of the amino group of one amino acid and the carboxyl group of another amino acid (105). Peptides serve various biological functions in the body, such as acting as hormones, enzymes and antibodies, and play key roles in regulating physiological processes (106). Furthermore, peptides hold promise for diagnosing and treating diseases, with specific peptides acting as biomarkers for cancers and neurodegenerative diseases, thereby aiding in early diagnosis and prognostic evaluation (107,108). For instance, a peptide known as MDANP has been shown to protect mice from necrotizing enterocolitis by modulating the PERK-eIF2α-QRICH1 signaling pathway (107). Similarly, Zhong et al (109) developed a peptide drug delivered via specific nanotechnology carriers, which targets and treats triple-negative breast cancer with high anti-tumor efficacy and low toxicity. These studies underscore the extensive biological functions and application potential of peptides, which can influence disease progression through various mechanisms and occupy a significant position in the development of novel therapies (110).

CircRNA is a class of non-coding RNA molecules with a closed-loop structure, characterized by high stability and tissue specificity. Studies suggested that circRNAs, besides acting as miRNA sponges or interacting with RNA-binding proteins to regulate gene expression, can also translate peptides through their ORF, thereby participating in the regulation of diseases such as cancer (32,67,111). These circRNA-encoded peptides possess diverse functions, including promoting or inhibiting the occurrence and development of tumors. For instance, certain circRNAs are translated independently of the canonical 5′ cap and 3′ poly(A) tail through mechanisms such as IRES and m6A modifications. The peptides encoded by these circRNAs regulate tumor progression by modulating pathways such as Yap-Hippo and Wnt/β-catenin, or through phosphorylation and ubiquitination of specific molecules (29,112). Furthermore, these peptides have been identified as novel tumor biomarkers and prognostic factors, useful for early tumor screening and personalized treatment strategies (113).

Notably, circRNA-encoded peptides have emerged as promising candidates for anti-tumor drug development, owing to their regulatory roles in key signaling pathways. For instance, in digestive system cancers, they influence key processes such as tumor cell proliferation, migration and apoptosis through the regulation of signaling pathways (113,114). Overall, circRNA-encoded peptides play crucial roles in tumor pathology but also show immense potential as novel biomarkers for diagnosis, therapy and prognosis assessment (14,115). Future research should focus on elucidating the precise mechanisms of circRNA-encoded peptides, facilitating their translation into clinical applications such as precision oncology.

Potential of circRNA-encoded peptides as therapeutic targets

CircRNAs, closed-loop non-coding single-stranded RNAs, are increasingly recognized for their diverse biological functions in human diseases (116). Studies revealed that certain circRNAs, apart from serving as miRNA sponges or templates for protein translation, can encode biologically active peptides through unique mechanisms such as IRES or m6A modifications (117-119). These circRNA-encoded peptides are involved in regulating cellular growth, migration, apoptosis and drug resistance. For instance, the peptide Aβ175 encoded by circAβ-a is implicated in the pathogenesis of Alzheimer's disease (AD), highlighting these peptides as promising therapeutic targets (117). Additionally, circMRPS35-168aa expression is upregulated in response to chemotherapy drugs, contributing to hepatocellular carcinoma resistance (120). In colorectal cancer, the peptide circMAPK14-175aa, by competitively binding MKK6, inhibits cancer progression and metastasis (99). Studies have also shown that the peptide SHPRH-146aa encoded by circ-SHPRH induces apoptosis in neuroblastoma cells, demonstrating its potential as a therapeutic agent for neurodegenerative diseases (121).

The high disease relevance and regulatory complexity of circRNA-encoded peptides provide possibilities for developing new biomarkers and therapeutic approaches. However, the current understanding of these peptides' functions and mechanisms of action remains relatively limited, necessitating further research to explore their precise roles in disease onset and how to effectively utilize these findings clinically (118). Such research not only aids in a deeper understanding of circRNA functions but may also advance translational medicine, offering new strategies for disease diagnosis and treatment.

Drug development and therapeutic strategies for circRNA-encoded peptides

In recent years, circRNAs have become a focal point in drug development and therapeutic strategies due to their unique structure and function. The closed-loop structure of circRNAs imparts higher stability and resistance to degradation in vivo, offering substantial potential for pharmaceutical applications (122). Research has shown that the peptide circFBXW7-185aa, encoded by circFBXW7, interacts with β-catenin, reducing its stability and promoting its ubiquitination, thereby inhibiting Wnt signaling pathway activation. This mechanism aids in enhancing the sensitivity to tyrosine kinase inhibitors in lung adenocarcinoma and reversing resistance (123). Another example is the peptide β-TrCP-343aa, encoded by circ-β-TrCP, which modulates the NRF2-mediated antioxidative pathway, promoting resistance to trastuzumab in HER2-positive breast cancer (104). In addition, the CAPG-171aa peptide encoded by circCAPG plays a crucial role in the pathogenesis of triple-negative breast cancer by activating the MEKK2-MEK1/2-ERK1/2 signaling pathway, enhancing tumor proliferation and metastasis (74).

CircRNA-encoded peptides also facilitate the development of novel diagnostic and prognostic markers. For instance, a peptide encoded by circβ-catenin can regulate the expression of β-catenin, thereby influencing the malignant phenotype of non-small cell lung cancer (124). In AD, circRNA-encoded amyloid β peptides provide new mechanisms for understanding the disease's pathogenesis (117). Furthermore, circRNA-encoded peptides show potential in treating metabolic diseases. For instance, the SLC9A6-126aa peptide encoded by circ-SLC9A6 modulates H4K16ac-mediated CD36 transcription, influencing lipid metabolism and offering a novel target for treating non-alcoholic fatty liver disease (125).

Overall, the prospects for circRNA-encoded peptides in overcoming cancer and anti-cancer drug resistance are broad. With deeper research into the functions and mechanisms of circRNA-encoded peptides, these molecules are expected to become important tools in the next generation of drug development, bringing innovative strategies for disease treatment.

Research strategy of circRNA-encoded peptides in NPC

Research has shown that EBV circBART2.2 can promote tumor immune escape by upregulating PD-L1 (55), while EBV circRPMS1 drives tumor progression in EBV-associated gastric cancer through Sam68-dependent METTL3 activation (47). These findings suggest that targeting EBV-encoded circRNAs, such as through antisense oligonucleotides or small molecule inhibitors, may become an effective strategy for intervening in NPC. In addition, LMP1 can regulate the expression of host circRNA through the NF-κB pathway (126), but the direct interaction mechanism between circRNA and LMP1 still needs further validation.

High-frequency mutated genes in NPC, such as TRAF3 and CYLD, may affect the biological function of circRNA. CYLD deficiency can inhibit cell apoptosis through NDRG1-dependent pathways (86) and enhance PFKFB3-mediated metabolic reprogramming (83). In addition, TRAF3 deficiency is associated with abnormal activation of the NF-κB pathway (127), but whether it regulates circRNA translation efficiency through m6A modification remains to be clarified. The correlation between TRAF3/CYLD mutations and circRNA peptide expression in patients with NPC can provide molecular evidence for targeted interventions through sequencing analysis.

The NPC organoid model has been successfully used to simulate the TME, such as CD70-CD27 interaction-mediated regulatory T-cell activation (128). In addition, EBV circLMP2A promotes angiogenesis through the KHSRP/VHL/HIF1α axis under hypoxic conditions (129), suggesting that organoid or patient-derived xenograft models can be used to validate the regulatory effect of circRNA peptides on the NF-κB/JAK-STAT pathway. For instance, the function of circARHGAP35 in NPC remains to be clarified and further research using gene editing models is needed.

The detection of circRNA-encoded peptides may become a new strategy for NPC diagnosis. For instance, circRNF13 inhibits NPC metastasis through SUMO2 (130), and its peptide segment may serve as a serum biomarker. In terms of treatment, monoclonal antibodies targeting circBART2.2 or vaccines that bind to EBV antigen epitopes may enhance the efficacy of immunotherapy (55). In addition, circIPO7 mediates cisplatin resistance by promoting YBX1 nuclear translocation (131), suggesting that its peptide segments can serve as targets for combination therapy.

Existing research has clarified the oncogenic role of EBV circRNA in NPC, but the specific mechanisms and translational application of circRNA peptides still require to be further explored. Future research needs to combine organoid models, high-frequency mutation gene analysis and clinical sample validation to promote the application of circRNA peptides in the diagnosis and treatment of NPC.

Current challenges and future perspectives

Technical challenges in circRNA-encoded peptide research

The field of circRNA-encoded peptides has garnered widespread attention due to its technical challenges and research advancements. For instance, studies have shown that the peptide circMAP3K4-455aa, translated from circMAP3K4 via m6A modification, interacts with AIF, inhibiting apoptosis in hepatocellular carcinoma, highlighting its potential in the context of RNA-based therapeutic development (132). Additionally, Lu et al (133) reviewed the role of circRNAs in translation, emphasizing the importance of IRES and m6A modifications in cap-independent translation, and showcased how modern high-throughput sequencing technologies and bioinformatics tools can explore the coding potential of circRNAs.

Despite these advancements, several key challenges remain in the study of circRNAs' coding functions. First, identifying and validating circRNAs with coding potential is particularly challenging, requiring advanced bioinformatics analysis and experimental validation (134). Furthermore, elucidating the biological functions and mechanisms of action of these peptides involves complex biochemical and molecular biology techniques (135). Lastly, translating these findings into clinical applications, such as developing targeted cancer therapies based on circRNA-encoded peptides, remains a significant research challenge (69,136).

In conclusion, although this is an emerging research area, the potential for circRNA-encoded peptides to bridge basic biology and translational medicine is gradually being recognized. Continued efforts are needed to elucidate their biological relevance and therapeutic value (137).

Future directions in research on NPC-related circRNA-encoded peptides

NPC is a malignant tumor with unique epidemiological and pathological features, including a close association with EBV infection and significant immune infiltration (138). Although advances in radiotherapy and chemotherapy have improved patient prognosis (139,140), challenges such as distant metastasis, recurrence, and drug resistance still exist (141). The study of circRNAs encoding peptides is becoming a promising frontier with potential relevance to these issues (137). However, research directly linking circRNA encoded peptides with NPC is still limited, which points to a clear direction for future research.

Recent advances have shown that certain circRNAs can produce bioactive peptides with tumor regulatory functions in other cancers. For instance, circFBXW7 and circGSPT1 encode peptides that inhibit cancer and gastric cancer tumor growth, respectively (142,143). These findings emphasize the importance of identifying and characterizing circRNAs in NPC that may also have coding potential, potentially revealing new tumor inhibitors or oncogenes specific to this cancer type.

In addition, technology platforms such as ribosome profiling and mass spectrometry have been proven to effectively detect circRNA translation events (137). Applying these techniques to NPC tissue and cell models may uncover novel circular RNA-encoded peptides that are uniquely expressed or dysregulated in NPC, thereby expanding the current molecular landscape of the disease.

Meanwhile, circRNA-based methods have been explored for therapeutic applications in other diseases. For example, it has been reported that circMIB2 exerts therapeutic effects by encoding a new protein in infectious diseases (136). Although not in the context of cancer, it provides a methodological basis for exploring the therapeutic delivery of circRNA-encoded peptides in preclinical NPC models in future research.

Finally, considering the different geographical distribution and region-dependent susceptibility of NPC (138), future research should explore the differences in circRNA expression and translation in patient populations, which may lead to changes in tumor biology and treatment response. Such studies may support the development of geographic region-dependent biomarkers or therapeutic strategies in NPC.

Conclusion

NPC is an epithelial tumor closely associated with EBV infection. Current evidence suggests that circRNA may influence gene regulatory networks in NPC, potentially affecting cellular processes such as proliferation, migration and metabolism through various mechanisms. In addition to regulating gene expression, certain circRNAs have been found to encode functional peptides. Although direct research on circRNA-encoded peptides in NPC remains limited, studies in other cancers have provided valuable insights into their potential roles. Future investigations should aim to clarify whether these peptides contribute to NPC development and progression, and to assess their value as diagnostic or prognostic biomarkers.

Availability of data and materials

Not applicable.

Authors' contributions

WX was involved in the study's conceptualization, methodology and writing-original draft. ZM participated in investigation, formal analysis and writing-original draft. WG was responsible for software, methodology and writing-review and editing. SF provided resources and supervision and contributed in writing-review and editing. XC was involved in in project administration, funding acquisition and writing-review and editing. All authors have read and approved the final version of the manuscript.

Ethics approval and consent to participate

Not applicable.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Acknowledgements

Not applicable.

Funding

This work was supported by the National Natural Science Foundation of China (grant no. 82360408).

References

1 

Huang H, Yao Y, Deng X, Huang Z, Chen Y, Wang Z, Hong H, Huang H and Lin T: Immunotherapy for nasopharyngeal carcinoma: Current status and prospects (Review). Int J Oncol. 63:972023. View Article : Google Scholar : PubMed/NCBI

2 

Guan S, Wei J, Huang L and Wu L: Chemotherapy and chemo-resistance in nasopharyngeal carcinoma. Eur J Med Chem. 207:1127582020. View Article : Google Scholar : PubMed/NCBI

3 

Chang ET, Ye W, Zeng YX and Adami HO: The evolving epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev. 30:1035–1047. 2021. View Article : Google Scholar : PubMed/NCBI

4 

Li W, Duan X, Chen X, Zhan M, Peng H, Meng Y, Li X, Li XY, Pang G and Dou X: Immunotherapeutic approaches in EBV-associated nasopharyngeal carcinoma. Front Immunol. 13:10795152022. View Article : Google Scholar

5 

Cantù G: Nasopharyngeal carcinoma. A 'different' head and neck tumour. Part B: Treatment, prognostic factors, and outcomes. Acta Otorhinolaryngol Ital. 43:155–169. 2023. View Article : Google Scholar

6 

Juarez-Vignon Whaley JJ, Afkhami M, Onyshchenko M, Massarelli E, Sampath S, Amini A, Bell D and Villaflor VM: Recurrent/metastatic nasopharyngeal carcinoma treatment from present to future: Where are we and where are we heading? Curr Treat Options Oncol. 24:1138–1166. 2023. View Article : Google Scholar : PubMed/NCBI

7 

Li W, Xu R, Zhu B, Wang H, Zhang H, Hu L, Li H, Sun X, Yu H and Wang D: Circular RNAs: Functions and mechanisms in nasopharyngeal carcinoma. Head Neck. 44:494–504. 2022. View Article : Google Scholar

8 

Chen RX, Liu HL, Yang LL, Kang FH, Xin LP, Huang LR, Guo QF and Wang YL: Circular RNA circRNA_0000285 promotes cervical cancer development by regulating FUS. Eur Rev Med Pharmacol Sci. 23:8771–8778. 2019.PubMed/NCBI

9 

Mo Y, Wang Y, Wang Y, Deng X, Yan Q, Fan C, Zhang S, Zhang S, Gong Z, Shi L, et al: Circular RNA circPVT1 promotes nasopharyngeal carcinoma metastasis via the β-TrCP/c-Myc/SRSF1 positive feedback loop. Mol Cancer. 21:1922022. View Article : Google Scholar

10 

Li Q, Zhao YH, Xu C, Liang YL, Zhao Y, He QM, Li JY, Chen KL, Qiao H, Liu N, et al: Chemotherapy-induced senescence reprogramming promotes nasopharyngeal carcinoma metastasis by circRNA-Mediated PKR activation. Adv Sci (Weinh). 10:e22056682023. View Article : Google Scholar : PubMed/NCBI

11 

Zhang D, Huang H, Sun Y, Cheng F, Zhao S, Liu J and Sun P: CircHIPK2 promotes proliferation of nasopharyngeal carcinoma by down-regulating HIPK2. Transl Cancer Res. 11:2348–2358. 2022. View Article : Google Scholar : PubMed/NCBI

12 

Liu H, Fang D, Zhang C, Zhao Z, Liu Y, Zhao S, Zhang N and Xu J: Circular MTHFD2L RNA-encoded CM-248aa inhibits gastric cancer progression by targeting the SET-PP2A interaction. Mol Ther. 31:1739–1755. 2023. View Article : Google Scholar : PubMed/NCBI

13 

Geng X, Wang J, Zhang C, Zhou X, Jing J and Pan W: Circular RNA circCOL6A3_030 is involved in the metastasis of gastric cancer by encoding polypeptide. Bioengineered. 12:8202–8216. 2021. View Article : Google Scholar : PubMed/NCBI

14 

Li Y, Wang Z, Su P, Liang Y, Li Z, Zhang H, Song X, Han D, Wang X, Liu Y, et al: circ-EIF6 encodes EIF6-224aa to promote TNBC progression via stabilizing MYH9 and activating the Wnt/beta-catenin pathway. Mol Ther. 30:415–430. 2022. View Article : Google Scholar :

15 

Xiong L, Liu HS, Zhou C, Yang X, Huang L, Jie HQ, Zeng ZW, Zheng XB, Li WX, Liu ZZ, et al: A novel protein encoded by circINSIG1 reprograms cholesterol metabolism by promoting the ubiquitin-dependent degradation of INSIG1 in colorectal cancer. Mol Cancer. 22:722023. View Article : Google Scholar : PubMed/NCBI

16 

Chen M, Yan C and Zhao X: Research progress on circular RNA in glioma. Front Oncol. 11:7050592021. View Article : Google Scholar : PubMed/NCBI

17 

Yuan W, Zhang X and Cong H: Advances in the protein-encoding functions of circular RNAs associated with cancer (review). Oncol Rep. 50:1602023. View Article : Google Scholar

18 

Fang N, Ding GW, Ding H, Li J, Liu C, Lv L and Shi YJ: Research progress of circular RNA in gastrointestinal tumors. Front Oncol. 11:6652462021. View Article : Google Scholar : PubMed/NCBI

19 

Zhang X, Lu N, Wang L, Wang Y, Li M, Zhou Y, Yan H, Cui M, Zhang M and Zhang L: Circular RNAs and esophageal cancer. Cancer Cell Int. 20:3622020. View Article : Google Scholar : PubMed/NCBI

20 

Zhu G, Chang X, Kang Y, Zhao X, Tang X, Ma C and Fu S: CircRNA: A novel potential strategy to treat thyroid cancer (review). Int J Mol Med. 48:2012021. View Article : Google Scholar : PubMed/NCBI

21 

Tang Q and Hann SS: Biological roles and mechanisms of circular RNA in human cancers. Onco Targets Ther. 13:2067–2092. 2020. View Article : Google Scholar : PubMed/NCBI

22 

Zhang Y, Luo J, Yang W and Ye WC: CircRNAs in colorectal cancer: Potential biomarkers and therapeutic targets. Cell Death Dis. 14:3532023. View Article : Google Scholar : PubMed/NCBI

23 

Galardi A, Colletti M, Palma A and Di Giannatale A: An update on circular RNA in pediatric cancers. Biomedicines. 11:362022. View Article : Google Scholar

24 

Zhu Y, Huang G, Li S, Xiong H, Chen R, Zuo L and Liu H: CircSMARCA5: A key circular RNA in various human diseases. Front Genet. 13:9213062022. View Article : Google Scholar : PubMed/NCBI

25 

Hwang HJ and Kim YK: Molecular mechanisms of circular RNA translation. Exp Mol Med. 56:1272–1280. 2024. View Article : Google Scholar : PubMed/NCBI

26 

Prats AC, David F, Diallo LH, Roussel E, Tatin F, Garmy-Susini B and Lacazette E: Circular RNA, the key for translation. Int J Mol Sci. 21:85912020. View Article : Google Scholar : PubMed/NCBI

27 

Wang Y, Wu C, Du Y, Li Z, Li M, Hou P, Shen Z, Chu S, Zheng J and Bai J: Expanding uncapped translation and emerging function of circular RNA in carcinomas and noncarcinomas. Mol Cancer. 21:132022. View Article : Google Scholar : PubMed/NCBI

28 

Wen SY, Qadir J and Yang BB: Circular RNA translation: Novel protein isoforms and clinical significance. Trends Mol Med. 28:405–420. 2022. View Article : Google Scholar : PubMed/NCBI

29 

Zhang L, Gao H, Li X, Yu F and Li P: The important regulatory roles of circRNA-encoded proteins or peptides in cancer pathogenesis (review). Int J Oncol. 64:192024. View Article : Google Scholar :

30 

Lin H, Wang Y, Wang P, Long F and Wang T: Mutual regulation between N6-methyladenosine (m6A) modification and circular RNAs in cancer: Impacts on therapeutic resistance. Mol Cancer. 21:1482022. View Article : Google Scholar : PubMed/NCBI

31 

Chen YG, Chen R, Ahmad S, Verma R, Kasturi SP, Amaya L, Broughton JP, Kim J, Cadena C, Pulendran B, et al: N6-Methyladenosine modification controls circular RNA immunity. Mol Cell. 76:96–109.e9. 2019. View Article : Google Scholar : PubMed/NCBI

32 

Lei M, Zheng G, Ning Q, Zheng J and Dong D: Translation and functional roles of circular RNAs in human cancer. Mol Cancer. 19:302020. View Article : Google Scholar : PubMed/NCBI

33 

Sinha T, Panigrahi C, Das D and Chandra Panda A: Circular RNA translation, a path to hidden proteome. Wiley Interdiscip Rev RNA. 13:e16852022. View Article : Google Scholar :

34 

Liu Y, Li Z, Zhang M, Zhou H, Wu X, Zhong J, Xiao F, Huang N, Yang X, Zeng R, et al: Rolling-translated EGFR variants sustain EGFR signaling and promote glioblastoma tumorigenicity. Neuro Oncol. 23:743–756. 2021. View Article : Google Scholar :

35 

Misir S, Wu N and Yang BB: Specific expression and functions of circular RNAs. Cell Death Differ. 29:481–491. 2022. View Article : Google Scholar : PubMed/NCBI

36 

Chen X, Zhou M, Yant L and Huang C: Circular RNA in disease: Basic properties and biomedical relevance. Wiley Interdiscip Rev RNA. 13:e17232022. View Article : Google Scholar : PubMed/NCBI

37 

Wang Z, Sun A, Yan A, Yao J, Huang H, Gao Z, Han T, Gu J, Li N, Wu H and Li K: Circular RNA MTCL1 promotes advanced laryngeal squamous cell carcinoma progression by inhibiting C1QBP ubiquitin degradation and mediating beta-catenin activation. Mol Cancer. 21:922022. View Article : Google Scholar : PubMed/NCBI

38 

Chen L and Shan G: CircRNA in cancer: Fundamental mechanism and clinical potential. Cancer Lett. 505:49–57. 2021. View Article : Google Scholar : PubMed/NCBI

39 

Zhou WY, Cai ZR, Liu J, Wang DS, Ju HQ and Xu RH: Circular RNA: Metabolism, functions and interactions with proteins. Mol Cancer. 19:1722020. View Article : Google Scholar : PubMed/NCBI

40 

Huang A, Zheng H, Wu Z, Chen M and Huang Y: Circular RNA-protein interactions: Functions, mechanisms, and identification. Theranostics. 10:3503–3517. 2020. View Article : Google Scholar : PubMed/NCBI

41 

Yang J, Gong Y, Jiang Q, Liu L, Li S, Zhou Q, Huang F and Liu Z: Circular RNA expression profiles in nasopharyngeal carcinoma by sequence analysis. Front Oncol. 10:6012020. View Article : Google Scholar : PubMed/NCBI

42 

Huang J, Cai Y, Guo L, Huang W, Yan J, Lai J, Wang Y, Jiang D and Peng L: hsa_circ_0136839 regulates the malignant phenotypes of nasopharyngeal carcinoma via the Wnt/β-catenin signaling pathway. Pathol Res Pract. 245:1544332023. View Article : Google Scholar

43 

Kamali MJ, Salehi M, Mostafavi M, Morovatshoar R, Akbari M, Latifi N, Barzegari O, Ghadimi F and Daraei A: Hijacking and rewiring of host CircRNA/miRNA/mRNA competitive endogenous RNA (ceRNA) regulatory networks by oncoviruses during development of viral cancers. Rev Med Virol. 34:e25302024. View Article : Google Scholar : PubMed/NCBI

44 

Wu H, Liu Y, Duan H, Fan X, Wang Y, Song J, Han J, Yang M, Lu L and Nie G: Identification of differentially expressed circular RNAs in human nasopharyngeal carcinoma. Cancer Biomark. 29:483–492. 2020. View Article : Google Scholar : PubMed/NCBI

45 

Zhou Z, Xu F and Zhang T: Circular RNA COL1A1 promotes Warburg effect and tumor growth in nasopharyngeal carcinoma. Discov Oncol. 15:1202024. View Article : Google Scholar : PubMed/NCBI

46 

Yu KH, Shi CH, Wang B, Chow SH, Chung GT, Lung RW, Tan KE, Lim YY, Tsang AC, Lo KW and Yip KY: Quantifying full-length circular RNAs in cancer. Genome Res. 31:2340–2353. 2021. View Article : Google Scholar : PubMed/NCBI

47 

Zhang S, Li Y, Xin S, Yang L, Jiang M, Xin Y, Wang Y, Yang J and Lu J: Insight into LncRNA- and CircRNA-mediated CeRNAs: Regulatory network and implications in nasopharyngeal Carcinoma-A narrative literature review. Cancers (Basel). 14:45642022. View Article : Google Scholar : PubMed/NCBI

48 

Zhou X, Yuan G, Wu Y, Yan S, Jiang Q and Tang S: EIF4A3-induced circFIP1L1 represses miR-1253 and promotes radiosensitivity of nasopharyngeal carcinoma. Cell Mol Life Sci. 79:3572022. View Article : Google Scholar : PubMed/NCBI

49 

Li H, You J, Xue H, Tan X and Chao C: CircCTDP1 promotes nasopharyngeal carcinoma progression via a microRNA-320b/HOXA10/TGFβ2 pathway. Int J Mol Med. 45:836–846. 2020.PubMed/NCBI

50 

Lin J, Qin H, Han Y, Li X, Zhao Y and Zhai G: CircNRIP1 modulates the miR-515-5p/IL-25 Axis to control 5-Fu and cisplatin resistance in nasopharyngeal carcinoma. Drug Des Devel Ther. 15:323–330. 2021. View Article : Google Scholar : PubMed/NCBI

51 

Yin L, Chen J, Ma C, Pei S, Du M, Zhang Y, Feng Y, Yin R, Bian X, He X, et al: Hsa_circ_0046263 functions as a ceRNA to promote nasopharyngeal carcinoma progression by upregulating IGFBP3. Cell Death Dis. 11:5622020. View Article : Google Scholar : PubMed/NCBI

52 

Duan ZN, Dong CG and Liu JH: Circ-ABCB10 promotes growth and metastasis of nasopharyngeal carcinoma by upregulating ROCK1. Eur Rev Med Pharmacol Sci. 24:12208–12215. 2020.PubMed/NCBI

53 

Chen H, Shi X, Ren L, Wan Y, Zhuo H, Zeng L, Sangdan W and Wang F: Screening of core genes and prediction of ceRNA regulation mechanism of circRNAs in nasopharyngeal carcinoma by bioinformatics analysis. Pathol Oncol Res. 29:16109602023. View Article : Google Scholar : PubMed/NCBI

54 

Li S and Wang Q: Hsa_circ_0081534 increases the proliferation and invasion of nasopharyngeal carcinoma cells through regulating the miR-508-5p/FN1 axis. Aging (Albany NY). 12:20645–20657. 2020. View Article : Google Scholar : PubMed/NCBI

55 

Ge J, Wang J, Xiong F, Jiang X, Zhu K, Wang Y, Mo Y, Gong Z, Zhang S, He Y, et al: Epstein-Barr Virus-encoded circular RNA CircBART2.2 promotes immune escape of nasopharyngeal carcinoma by regulating PD-L1. Cancer Res. 81:5074–5088. 2021. View Article : Google Scholar : PubMed/NCBI

56 

Ka-Yue Chow L, Lai-Shun Chung D, Tao L, Chan KF, Tung SY, Cheong Ngan RK, Ng WT, Wing-Mui Lee A, Yau CC, Lai-Wan Kwong D, et al: Epigenomic landscape study reveals molecular subtypes and EBV-associated regulatory epigenome reprogramming in nasopharyngeal carcinoma. EBioMedicine. 86:1043572022. View Article : Google Scholar : PubMed/NCBI

57 

Zeng C, Qiao M, Chen Y and Xie H: EBV-positive glycoproteins associated with nasopharyngeal carcinoma. Pathol Res Pract. 260:1554272024. View Article : Google Scholar : PubMed/NCBI

58 

Chen H, Duan X, Deng X, Huang Y, Zhou X, Zhang S, Zhang X, Liu P, Yang C, Liu G, et al: EBV-Upregulated B7-H3 inhibits NK cell-mediated antitumor function and contributes to nasopharyngeal carcinoma progression. Cancer Immunol Res. 11:830–846. 2023. View Article : Google Scholar : PubMed/NCBI

59 

Yuan L, Li S, Chen Q, Xia T, Luo D, Li L, Liu S, Guo S, Liu L, Du C, et al: EBV infection-induced GPX4 promotes chemoresistance and tumor progression in nasopharyngeal carcinoma. Cell Death Differ. 29:1513–1527. 2022. View Article : Google Scholar : PubMed/NCBI

60 

Shi F, Shang L, Zhou M, Lv C, Li Y, Luo C, Liu N, Lu J, Tang M, Luo X, et al: Epstein-Barr Virus-driven metabolic alterations contribute to the viral lytic reactivation and tumor progression in nasopharyngeal carcinoma. J Med Virol. 96:e296342024. View Article : Google Scholar : PubMed/NCBI

61 

Wan X, Liu Y, Peng Y, Wang J, Yan SM, Zhang L, Wu W, Zhao L, Chen X, Ren K, et al: Primary and orthotopic murine models of nasopharyngeal carcinoma reveal molecular mechanisms underlying its Malignant Progression. Adv Sci (Weinh). 11:e24031612024. View Article : Google Scholar : PubMed/NCBI

62 

Peng X, Zhou Y, Tao Y and Liu S: Nasopharyngeal carcinoma: The role of the EGFR in Epstein-Barr virus infection. Pathogens. 10:11132021. View Article : Google Scholar : PubMed/NCBI

63 

Su ZY, Siak PY, Lwin YY and Cheah SC: Epidemiology of nasopharyngeal carcinoma: Current insights and future outlook. Cancer Metastasis Rev. 43:919–939. 2024. View Article : Google Scholar : PubMed/NCBI

64 

Campion NJ, Ally M, Jank BJ, Ahmed J and Alusi G: The molecular march of primary and recurrent nasopharyngeal carcinoma. Oncogene. 40:1757–1774. 2021. View Article : Google Scholar : PubMed/NCBI

65 

Xu M, Feng R, Liu Z, Zhou X, Chen Y, Cao Y, Valeri L, Li Z, Liu Z, Cao SM, et al: Host genetic variants, Epstein-Barr virus subtypes, and the risk of nasopharyngeal carcinoma: Assessment of interaction and mediation. Cell Genom. 4:1004742024. View Article : Google Scholar : PubMed/NCBI

66 

Ren L, Jiang Q, Mo L, Tan L, Dong Q, Meng L, Yang N and Li G: Mechanisms of circular RNA degradation. Commun Biol. 5:13552022. View Article : Google Scholar : PubMed/NCBI

67 

Wang J, Zhu S, Meng N, He Y, Lu R and Yan GR: ncRNA-encoded peptides or proteins and cancer. Mol Ther. 27:1718–1725. 2019. View Article : Google Scholar : PubMed/NCBI

68 

Peng Y, Xu Y, Zhang X, Deng S, Yuan Y, Luo X, Hossain MT, Zhu X, Du K, Hu F, et al: A novel protein AXIN1-295aa encoded by circAXIN1 activates the Wnt/β-catenin signaling pathway to promote gastric cancer progression. Mol Cancer. 20:1582021. View Article : Google Scholar

69 

Huang B, Ren J, Ma Q, Yang F, Pan X, Zhang Y, Liu Y, Wang C, Zhang D, Wei L, et al: A novel peptide PDHK1-241aa encoded by circPDHK1 promotes ccRCC progression via interacting with PPP1CA to inhibit AKT dephosphorylation and activate the AKT-mTOR signaling pathway. Mol Cancer. 23:342024. View Article : Google Scholar : PubMed/NCBI

70 

Li Y, Wang Z, Yang J, Sun Y, He Y, Wang Y, Chen X, Liang Y, Zhang N, Wang X, et al: CircTRIM1 encodes TRIM1-269aa to promote chemoresistance and metastasis of TNBC via enhancing CaM-dependent MARCKS translocation and PI3K/AKT/mTOR activation. Mol Cancer. 23:1022024. View Article : Google Scholar : PubMed/NCBI

71 

Jiang T, Xia Y, Lv J, Li B, Li Y, Wang S, Xuan Z, Xie L, Qiu S, He Z, et al: A novel protein encoded by circMAPK1 inhibits progression of gastric cancer by suppressing activation of MAPK signaling. Mol Cancer. 20:662021. View Article : Google Scholar : PubMed/NCBI

72 

Wang X, Jian W, Luo Q and Fang L: CircSEMA4B inhibits the progression of breast cancer by encoding a novel protein SEMA4B-211aa and regulating AKT phosphorylation. Cell Death Dis. 13:7942022. View Article : Google Scholar : PubMed/NCBI

73 

Wu X, Xiao S, Zhang M, Yang L, Zhong J, Li B, Li F, Xia X, Li X, Zhou H, et al: A novel protein encoded by circular SMO RNA is essential for Hedgehog signaling activation and glioblastoma tumorigenicity. Genome Biol. 22:332021. View Article : Google Scholar : PubMed/NCBI

74 

Song R, Guo P, Ren X, Zhou L, Li P, Rahman NA, Wołczyński S, Li X, Zhang Y, Liu M, et al: A novel polypeptide CAPG-171aa encoded by circCAPG plays a critical role in triple-negative breast cancer. Mol Cancer. 22:1042023. View Article : Google Scholar : PubMed/NCBI

75 

Wang L, Zheng W, Lv X, Song Y and Xu T: circMORC3-encoded novel protein negatively regulates antiviral immunity through synergizing with host gene MORC3. PLoS Pathog. 19:e10118942023. View Article : Google Scholar : PubMed/NCBI

76 

Huang W, Zhang L, Yang M, Wu X, Wang X, Huang W, Yuan L, Pan H, Wang Y, Wang Z, et al: Cancer-associated fibroblasts promote the survival of irradiated nasopharyngeal carcinoma cells via the NF-κB pathway. J Exp Clin Cancer Res. 40:872021. View Article : Google Scholar

77 

Zhang H, Deng S, Zhang J, Zhu G, Zhou J, Ye W, Wang Q, Wang Y, Zou B, Zhang P, et al: Single nucleotide polymorphisms within NFKBIA are associated with nasopharyngeal carcinoma susceptibility in Chinese Han population. Cytokine. 138:1553562021. View Article : Google Scholar

78 

Li XD, Zhong QL, Luo DJ, Liang QF, Qiu JQ, Du QH, Xiao L, Zhou YH, Long YB, Liu WQ, et al: RNF219 promotes nasopharyngeal carcinoma progression by activating the NF-κB pathway. Mol Biotechnol. 65:1318–1326. 2023. View Article : Google Scholar

79 

Chen X, Weng Y, Li Y, Fu W, Huang Z, Pan Y, Hong W, Lin W, Lin X and Qiu S: Upregulation of PNCK Promotes Metastasis and Angiogenesis via Activating NF-κB/VEGF pathway in nasopharyngeal carcinoma. J Oncol. 2022:85415822022.

80 

Ling J, Zhang L, Chang A, Huang Y, Ren J, Zhao H and Zhuo X: Overexpression of KITLG predicts unfavorable clinical outcomes and promotes lymph node metastasis via the JAK/STAT pathway in nasopharyngeal carcinoma. Lab Invest. 102:1257–1267. 2022. View Article : Google Scholar : PubMed/NCBI

81 

Kaisai T, Mantang Z, Tailei Y, Liying Z, Xiaoping C, Mingming J and Yi Z: Hsa_circ_0013561 promotes progression of nasopharyngeal carcinoma by activating JAK2/STAT3 signaling pathway. Braz J Otorhinolaryngol. 90:1013622024. View Article : Google Scholar

82 

Bruce JP, To KF, Lui VWY, Chung GTY, Chan YY, Tsang CM, Yip KY, Ma BBY, Woo JKS, Hui EP, et al: Whole-genome profiling of nasopharyngeal carcinoma reveals viral-host co-operation in inflammatory NF-κB activation and immune escape. Nat Commun. 12:41932021. View Article : Google Scholar

83 

Wang L, Lin Y, Zhou X, Chen Y, Li X, Luo W, Zhou Y and Cai L: CYLD deficiency enhances metabolic reprogramming and tumor progression in nasopharyngeal carcinoma via PFKFB3. Cancer Lett. 532:2155862022. View Article : Google Scholar : PubMed/NCBI

84 

Deng M, Dai W, Yu VZ, Tao L and Lung ML: Cylindromatosis lysine 63 deubiquitinase (CYLD) regulates NF-kB signaling pathway and modulates fibroblast and endothelial cells recruitment in nasopharyngeal carcinoma. Cancers (Basel). 12:19242020. View Article : Google Scholar : PubMed/NCBI

85 

Li Y, Shi F, Hu J, Xie L, Zhao L, Tang M, Luo X, Ye M, Zheng H, Zhou M, et al: Stabilization of p18 by deubiquitylase CYLD is pivotal for cell cycle progression and viral replication. NPJ Precis Oncol. 5:142021. View Article : Google Scholar : PubMed/NCBI

86 

Lin Y, Wang L, Luo W, Zhou X, Chen Y, Yang K, Liao J, Wu D and Cai L: CYLD Promotes apoptosis of nasopharyngeal carcinoma cells by regulating NDRG1. Cancer Manag Res. 12:10639–10649. 2020. View Article : Google Scholar : PubMed/NCBI

87 

Mizokami H, Okabe A, Choudhary R, Mima M, Saeda K, Fukuyo M, Rahmutulla B, Seki M, Goh BC, Kondo S, et al: Enhancer infestation drives tumorigenic activation of inactive B compartment in Epstein-Barr virus-positive nasopharyngeal carcinoma. EBioMedicine. 102:1050572024. View Article : Google Scholar : PubMed/NCBI

88 

Reffai A, Hori M, Adusumilli R, Bermudez A, Bouzoubaa A, Pitteri S, Bennani Mechita M and Mallick P: A proteomic analysis of nasopharyngeal carcinoma in a moroccan subpopulation. Cancers (Basel). 16:32822024. View Article : Google Scholar : PubMed/NCBI

89 

Xie T, Fu DJ, Li ZM, Lv DJ, Song XL, Yu YZ, Wang C, Li KJ, Zhai B, Wu J, et al: CircSMARCC1 facilitates tumor progression by disrupting the crosstalk between prostate cancer cells and tumor-associated macrophages via miR-1322/CCL20/CCR6 signaling. Mol Cancer. 21:1732022. View Article : Google Scholar : PubMed/NCBI

90 

Song J, Liu Q, Han L, Song T, Huang S, Zhang X, He Q, Liang C, Zhu S and Xiong B: Hsa_circ_0009092/miR-665/NLK signaling axis suppresses colorectal cancer progression via recruiting TAMs in the tumor microenvironment. J Exp Clin Cancer Res. 42:3192023. View Article : Google Scholar : PubMed/NCBI

91 

Miao Z, Li J, Wang Y, Shi M, Gu X, Zhang X, Wei F, Tang X, Zheng L and Xing Y: Hsa_circ_0136666 stimulates gastric cancer progression and tumor immune escape by regulating the miR-375/PRKDC Axis and PD-L1 phosphorylation. Mol Cancer. 22:2052023. View Article : Google Scholar : PubMed/NCBI

92 

Pan Z, Zhao R, Li B, Qi Y, Qiu W, Guo Q, Zhang S, Zhao S, Xu H, Li M, et al: EWSR1-induced circNEIL3 promotes glioma progression and exosome-mediated macrophage immunosuppressive polarization via stabilizing IGF2BP3. Mol Cancer. 21:162022. View Article : Google Scholar : PubMed/NCBI

93 

Zhang F, Jiang J, Qian H, Yan Y and Xu W: Exosomal circRNA: Emerging insights into cancer progression and clinical application potential. J Hematol Oncol. 16:672023. View Article : Google Scholar : PubMed/NCBI

94 

Zhou B, Mo Z, Lai G, Chen X, Li R, Wu R, Zhu J and Zheng F: Targeting tumor exosomal circular RNA cSERPINE2 suppresses breast cancer progression by modulating MALT1-NF-κB-IL-6 axis of tumor-associated macrophages. J Exp Clin Cancer Res. 42:482023. View Article : Google Scholar

95 

Li J, Song Y, Cai H, Zhou B and Ma J: Roles of circRNA dysregulation in esophageal squamous cell carcinoma tumor microenvironment. Front Oncol. 13:11532072023. View Article : Google Scholar : PubMed/NCBI

96 

Wang J, Lin Y, Jiang DH, Yang X and He XG: CircRNA ZNF609 promotes angiogenesis in nasopharyngeal carcinoma by regulating miR-145/STMN1 axis. Kaohsiung J Med Sci. 37:686–698. 2021. View Article : Google Scholar : PubMed/NCBI

97 

Zhu L, Liu Y, Yang Y, Mao XM and Yin ZD: CircRNA ZNF609 promotes growth and metastasis of nasopharyngeal carcinoma by competing with microRNA-150-5p. Eur Rev Med Pharmacol Sci. 23:2817–2826. 2019.PubMed/NCBI

98 

Saunders JT, Kumar S, Benavides-Serrato A, Holmes B, Benavides KE, Bashir MT, Nishimura RN and Gera J: Translation of circHGF RNA encodes an HGF protein variant promoting glioblastoma growth through stimulation of c-MET. J Neurooncol. 163:207–218. 2023. View Article : Google Scholar : PubMed/NCBI

99 

Wang L, Zhou J, Zhang C, Chen R, Sun Q, Yang P, Peng C, Tan Y, Jin C, Wang T, et al: A novel tumour suppressor protein encoded by circMAPK14 inhibits progression and metastasis of colorectal cancer by competitively binding to MKK6. Clin Transl Med. 11:e6132021. View Article : Google Scholar : PubMed/NCBI

100 

Zhang C, Zhou X, Geng X, Zhang Y, Wang J, Wang Y, Jing J, Zhou X and Pan W: Circular RNA hsa_circ_0006401 promotes proliferation and metastasis in colorectal carcinoma. Cell Death Dis. 12:4432021. View Article : Google Scholar : PubMed/NCBI

101 

Zheng X, Chen L, Zhou Y, Wang Q, Zheng Z, Xu B, Wu C, Zhou Q, Hu W, Wu C, et al: A novel protein encoded by a circular RNA circPPP1R12A promotes tumor pathogenesis and metastasis of colon cancer via Hippo-YAP signaling. Mol Cancer. 18:472019. View Article : Google Scholar : PubMed/NCBI

102 

Xie T, Yang Z, Xian S, Lin Q, Huang L and Ding Y: Hsa_circ_0008833 promotes COPD progression via inducing pyroptosis in bronchial epithelial cells. Exp Lung Res. 50:1–14. 2024. View Article : Google Scholar : PubMed/NCBI

103 

Li F, Cai Y, Deng S, Yang L, Liu N, Chang X, Jing L, Zhou Y and Li H: A peptide CORO1C-47aa encoded by the circular noncoding RNA circ-0000437 functions as a negative regulator in endometrium tumor angiogenesis. J Biol Chem. 297:1011822021. View Article : Google Scholar : PubMed/NCBI

104 

Wang S, Wang Y, Li Q, Li X, Feng X and Zeng K: The novel β-TrCP protein isoform hidden in circular RNA confers trastuzumab resistance in HER2-positive breast cancer. Redox Biol. 67:1028962023. View Article : Google Scholar

105 

Chadani Y, Sugata N, Niwa T, Ito Y, Iwasaki S and Taguchi H: Nascent polypeptide within the exit tunnel stabilizes the ribosome to counteract risky translation. EMBO J. 40:e1082992021. View Article : Google Scholar : PubMed/NCBI

106 

Wang P, Li W, Yang Y, Cheng N, Zhang Y, Zhang N, Yin Y, Tong L, Li Z and Luo J: A polypeptide inhibitor of calcineurin blocks the calcineurin-NFAT signalling pathway in vivo and in vitro. J Enzyme Inhib Med Chem. 37:202–210. 2022. View Article : Google Scholar

107 

Huo J, Zhang R, Wu X, Fu C, Hu J, Hu X, Sun W, Chen Z and Zhu X: Active polypeptide MDANP protect against necrotizing enterocolitis (NEC) by regulating the PERK-eIF2α-QRICH1 axis. Sci Rep. 13:229122023. View Article : Google Scholar

108 

Shubayev VI, Dolkas J, Catroli GF and Chernov AV: A human coronavirus OC43-derived polypeptide causes neuropathic pain. EMBO Rep. 23:e540692022. View Article : Google Scholar : PubMed/NCBI

109 

Zhong C, Li J, Liu S, Li W, Zhang Q, Zhao J, Xiong M, Bao Y and Yao Y: Nanoblock-mediated selective oncolytic polypeptide therapy for triple-negative breast cancer. Theranostics. 13:2800–2810. 2023. View Article : Google Scholar : PubMed/NCBI

110 

Höpfler M and Hegde RS: Control of mRNA fate by its encoded nascent polypeptide. Mol Cell. 83:2840–2855. 2023. View Article : Google Scholar : PubMed/NCBI

111 

Wu P, Mo Y, Peng M, Tang T, Zhong Y, Deng X, Xiong F, Guo C, Wu X, Li Y, et al: Emerging role of tumor-related functional peptides encoded by lncRNA and circRNA. Mol Cancer. 19:222020. View Article : Google Scholar : PubMed/NCBI

112 

Meng E, Deng J, Jiang R and Wu H: CircRNA-Encoded peptides or proteins as new players in digestive system neoplasms. Front Oncol. 12:9441592022. View Article : Google Scholar : PubMed/NCBI

113 

Ferreira HJ, Stevenson BJ, Pak H, Yu F, Almeida Oliveira J, Huber F, Taillandier-Coindard M, Michaux J, Ricart-Altimiras E, Kraemer AI, et al: Immunopeptidomics-based identification of naturally presented non-canonical circRNA-derived peptides. Nat Commun. 15:23572024. View Article : Google Scholar : PubMed/NCBI

114 

Khan FA, Nsengimana B, Khan NH, Song Z, Ngowi EE, Wang Y, Zhang W and Ji S: Chimeric Peptides/proteins encoded by circRNA: An update on mechanisms and functions in human cancers. Front Oncol. 12:7812702022. View Article : Google Scholar : PubMed/NCBI

115 

Ke SA, Zhao S, Liu Y, Zhuo Q, Tong X and Xu Y: Circular RNA-encoded peptides and proteins: Implications to cancer. Sheng Wu Gong Cheng Xue Bao. 38:3131–3140. 2022.In Chinese. PubMed/NCBI

116 

Li W, Liu JQ, Chen M, Xu J and Zhu D: Circular RNA in cancer development and immune regulation. J Cell Mol Med. 26:1785–1798. 2022. View Article : Google Scholar :

117 

Mo D, Li X, Raabe CA, Rozhdestvensky TS, Skryabin BV and Brosius J: Circular RNA encoded amyloid beta peptides-A novel putative player in Alzheimer's disease. Cells. 9:21962020. View Article : Google Scholar : PubMed/NCBI

118 

Liu H, Hao W, Yang J, Zhang Y, Wang X and Zhang C: Emerging roles and potential clinical applications of translatable circular RNAs in cancer and other human diseases. Genes Dis. 10:1994–2012. 2023. View Article : Google Scholar : PubMed/NCBI

119 

Zheng W, Wang L, Geng S and Xu T: CircYthdc2 generates polypeptides through two translation strategies to facilitate virus escape. Cell Mol Life Sci. 81:912024. View Article : Google Scholar : PubMed/NCBI

120 

Li P, Song R, Yin F, Liu M, Liu H, Ma S, Jia X, Lu X, Zhong Y, Yu L, et al: circMRPS35 promotes malignant progression and cisplatin resistance in hepatocellular carcinoma. Mol Ther. 30:431–447. 2022. View Article : Google Scholar :

121 

Gao J, Pan H, Li J, Jiang J and Wang W: A peptide encoded by the circular form of the SHPRH gene induces apoptosis in neuroblastoma cells. PeerJ. 12:e168062024. View Article : Google Scholar : PubMed/NCBI

122 

Liu X, Zhang Y, Zhou S, Dain L, Mei L and Zhu G: Circular RNA: An emerging frontier in RNA therapeutic targets, RNA therapeutics, and mRNA vaccines. J Control Release. 348:84–94. 2022. View Article : Google Scholar : PubMed/NCBI

123 

Li K, Peng ZY, Wang R, Li X, Du N, Liu DP, Zhang J, Zhang YF, Ma L, Sun Y, et al: Enhancement of TKI sensitivity in lung adenocarcinoma through m6A-dependent translational repression of Wnt signaling by circ-FBXW7. Mol Cancer. 22:1032023. View Article : Google Scholar : PubMed/NCBI

124 

Zhao W, Zhang Y and Zhu Y: Circular RNA circβ-catenin aggravates the malignant phenotype of non-small-cell lung cancer via encoding a peptide. J Clin Lab Anal. 35:e239002021. View Article : Google Scholar

125 

Wang Y, Tian X, Wang Z, Liu D, Zhao X, Sun X, Tu Z, Li Z, Zhao Y, Zheng S, et al: A novel peptide encoded by circ-SLC9A6 promotes lipid dyshomeostasis through the regulation of H4K16ac-mediated CD36 transcription in NAFLD. Clin Transl Med. 14:e18012024. View Article : Google Scholar : PubMed/NCBI

126 

Torres K, Landeros N, Wichmann IA, Polakovicova I, Aguayo F and Corvalan AH: EBV miR-BARTs and human lncRNAs: Shifting the balance in competing endogenous RNA networks in EBV-associated gastric cancer. Biochim Biophys Acta Mol Basis Dis. 1867:1660492021. View Article : Google Scholar : PubMed/NCBI

127 

Zhou Z, Li P, Zhang X, Xu J, Xu J, Yu S, Wang D, Dong W, Cao X, Yan H, et al: Mutational landscape of nasopharyngeal carcinoma based on targeted next-generation sequencing: Implications for predicting clinical outcomes. Mol Med. 28:552022. View Article : Google Scholar

128 

Gong L, Luo J, Zhang Y, Yang Y, Li S, Fang X, Zhang B, Huang J, Chow LK, Chung D, et al: Nasopharyngeal carcinoma cells promote regulatory T cell development and suppressive activity via CD70-CD27 interaction. Nat Commun. 14:19122023. View Article : Google Scholar : PubMed/NCBI

129 

Du Y, Zhang JY, Gong LP, Feng ZY, Wang D, Pan YH, Sun LP, Wen JY, Chen GF, Liang J, et al: Hypoxia-induced ebv-circLMP2A promotes angiogenesis in EBV-associated gastric carcinoma through the KHSRP/VHL/HIF1α/VEGFA pathway. Cancer Lett. 526:259–272. 2022. View Article : Google Scholar

130 

Mo Y, Wang Y, Zhang S, Xiong F, Yan Q, Jiang X, Deng X, Wang Y, Fan C, Tang L, et al: Circular RNA circRNF13 inhibits proliferation and metastasis of nasopharyngeal carcinoma via SUMO2. Mol Cancer. 20:1122021. View Article : Google Scholar : PubMed/NCBI

131 

Hong X, Li Q, Li J, Chen K, He Q, Zhao Y, Liang Y, Zhao Y, Qiao H, Liu N, et al: CircIPO7 promotes nasopharyngeal carcinoma metastasis and cisplatin chemoresistance by facilitating YBX1 nuclear localization. Clin Cancer Res. 28:4521–4535. 2022. View Article : Google Scholar : PubMed/NCBI

132 

Duan JL, Chen W, Xie JJ, Zhang ML, Nie RC, Liang H, Mei J, Han K, Xiang ZC, Wang FW, et al: A novel peptide encoded by N6-methyladenosine modified circMAP3K4 prevents apoptosis in hepatocellular carcinoma. Mol Cancer. 21:932022. View Article : Google Scholar : PubMed/NCBI

133 

Lu Y, Li Z, Lin C, Zhang J and Shen Z: Translation role of circRNAs in cancers. J Clin Lab Anal. 35:e238662021. View Article : Google Scholar : PubMed/NCBI

134 

Othoum G, Coonrod E, Zhao S, Dang HX and Maher CA: Pan-cancer proteogenomic analysis reveals long and circular noncoding RNAs encoding peptides. NAR Cancer. 2:zcaa0152020. View Article : Google Scholar : PubMed/NCBI

135 

Chen Q, Shen H, Nie F and Sun M: A Whole new comprehension about ncRNA-Encoded Peptides/proteins in cancers. Cancers (Basel). 14:51962022. View Article : Google Scholar : PubMed/NCBI

136 

Zheng W, Wang L, Geng S, Yang L, Lv X, Xin S and Xu T: CircMIB2 therapy can effectively treat pathogenic infection by encoding a novel protein. Cell Death Dis. 14:5782023. View Article : Google Scholar : PubMed/NCBI

137 

Shi X, Liao S, Bi Z, Liu J, Li H and Feng C: Newly discovered circRNAs encoding proteins: Recent progress. Front Genet. 14:12646062023. View Article : Google Scholar : PubMed/NCBI

138 

Jiang J and Ying H: Revealing the crosstalk between nasopharyngeal carcinoma and immune cells in the tumor microenvironment. J Exp Clin Cancer Res. 41:2442022. View Article : Google Scholar

139 

Tang LL, Guo R, Zhang N, Deng B, Chen L, Cheng ZB, Huang J, Hu WH, Huang SH, Luo WJ, et al: Effect of radiotherapy alone vs radiotherapy with concurrent chemoradiotherapy on survival without disease relapse in patients with Low-risk nasopharyngeal carcinoma: A randomized clinical trial. JAMA. 328:728–736. 2022. View Article : Google Scholar : PubMed/NCBI

140 

You R, Liu YP, Huang PY, Zou X, Sun R, He YX, Wu YS, Shen GP, Zhang HD, Duan CY, et al: Efficacy and safety of locoregional radiotherapy with chemotherapy vs chemotherapy alone in de novo metastatic nasopharyngeal carcinoma: A multicenter phase 3 randomized clinical trial. JAMA Oncol. 6:1345–1352. 2020. View Article : Google Scholar : PubMed/NCBI

141 

Toumi N, Ennouri S, Charfeddine I, Daoud J and Khanfir A: Prognostic factors in metastatic nasopharyngeal carcinoma. Braz J Otorhinolaryngol. 88:212–219. 2022. View Article : Google Scholar :

142 

Ye F, Gao G, Zou Y, Zheng S, Zhang L, Ou X, Xie X and Tang H: circFBXW7 inhibits malignant progression by sponging miR-197-3p and encoding a 185-aa protein in Triple-negative breast cancer. Mol Ther Nucleic Acids. 18:88–98. 2019. View Article : Google Scholar : PubMed/NCBI

143 

Hu F, Peng Y, Chang S, Luo X, Yuan Y, Zhu X, Xu Y, Du K, Chen Y, Deng S, et al: Vimentin binds to a novel tumor suppressor protein, GSPT1-238aa, encoded by circGSPT1 with a selective encoding priority to halt autophagy in gastric carcinoma. Cancer Lett. 545:2158262022. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

October-2025
Volume 67 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Xu W, Ma Z, Gong W, Fu S and Chen X: Functional mechanisms of circular RNA‑encoded peptides and future research strategies and directions in nasopharyngeal carcinoma (Review). Int J Oncol 67: 82, 2025.
APA
Xu, W., Ma, Z., Gong, W., Fu, S., & Chen, X. (2025). Functional mechanisms of circular RNA‑encoded peptides and future research strategies and directions in nasopharyngeal carcinoma (Review). International Journal of Oncology, 67, 82. https://doi.org/10.3892/ijo.2025.5788
MLA
Xu, W., Ma, Z., Gong, W., Fu, S., Chen, X."Functional mechanisms of circular RNA‑encoded peptides and future research strategies and directions in nasopharyngeal carcinoma (Review)". International Journal of Oncology 67.4 (2025): 82.
Chicago
Xu, W., Ma, Z., Gong, W., Fu, S., Chen, X."Functional mechanisms of circular RNA‑encoded peptides and future research strategies and directions in nasopharyngeal carcinoma (Review)". International Journal of Oncology 67, no. 4 (2025): 82. https://doi.org/10.3892/ijo.2025.5788