RBM8A promotes gastric cancer progression by binding with UPF3B to induce BBC3 mRNA degradation

Peng,Hang; Zhang,Long; Li,Fang; Jing,Xintao; Zhou,Jing; Cao,Li; Xu,Cuixiang; Wang,Jianhua; Huang,Chen

doi:10.3892/ijmm.2025.5572

RBM8A promotes gastric cancer progression by binding with UPF3B to induce BBC3 mRNA degradation

Authors:
- Hang Peng
- Long Zhang
- Fang Li
- Xintao Jing
- Jing Zhou
- Li Cao
- Cuixiang Xu
- Jianhua Wang
- Chen Huang
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Affiliations: Second Department of General Surgery, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China, Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, Department of Cell Biology and Genetics/Key Laboratory of Environment and Genes Related to Diseases, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China, Shaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China
Published online on: June 30, 2025 https://doi.org/10.3892/ijmm.2025.5572
Article Number: 131
Copyright: © Peng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

RNA metabolism is an important post‑transcriptional regulatory mode in organisms, and its process is cooperatively regulated by a variety of RNA‑binding proteins. RNA binding motif protein 8A (RBM8A), a regulator of mRNA stability that is implicated in cancer progression, serves an important role in processes such as RNA splicing, transport, translation and decay. However, to the best of our knowledge, its role in the occurrence and development of gastric cancer (GC), as well as its biological functions and molecular mechanisms remain unclear. In the present study, RBM8A expression was on average 1.4‑fold higher (P<0.05), with a maximum log2 fold change of 1.4 (2.6‑fold increase), in GC tissues compared with adjacent normal tissues, as determined by multiplex immunohistochemical analysis of tissue microarrays. In vitro, transfection of RBM8A small interfering RNAs significantly suppressed the proliferation of AGS and HGC27 cells and enhanced apoptosis. Specifically, annexin V‑positive AGS cells exhibited a 2.9‑fold increase with siRBM8A‑1 transfection and a 1.9‑fold increase with siRBM8A‑2 transfection, while annexin V‑positive HGC27 cells exhibited a 2.3‑fold increase with siRBM8A‑1 transfection and a 1.8‑fold increase with siRBM8A‑2 transfection (P<0.05). Using MKN45 cell lines and subcutaneous xenograft models, the present study revealed that RBM8A knockdown reduced subcutaneous tumor growth in nude mice by 51.5% in terms of volume and 62.4% in terms of weight (P<0.05). In terms of the mechanism, integrated mRNA‑sequencing (seq) and RNA immunoprecipitation (RIP)‑seq identified BCL2 binding component 3 (BBC3), a well‑characterized pro‑apoptotic gene, as a direct target of RBM8A. Further results of RIP‑quantitative PCR, fluorescence in situ hybridization‑immunofluorescence and RNA pulldown indicated the direct interaction between RBM8A and BBC3 mRNA. Actinomycin D assays demonstrated that RBM8A promoted BBC3 mRNA degradation. Subsequently, the co‑immunoprecipitation assay showed that RBM8A interacted with UPF3B to jointly regulate the stability of BBC3 mRNA. In conclusion, RBM8A inhibited apoptosis and promoted GC progression by interacting with UPF3B, leading to degradation of the pro‑apoptotic gene BBC3 mRNA. These findings highlighted that interfering with RBM8A expression, or disrupting the interactions between RBM8A and BBC3 mRNA or between RBM8A and UPF3B could serve as potential therapeutic strategies for GC.

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