EIF3B‑METTL3 complex promotes cell proliferation, invasion and EGFR/AKT signaling in cervical cancer

Zhang,Chao; Fan,Xiang; Yang,Jia; Zhu,Pengfeng

doi:10.3892/or.2025.8936

EIF3B‑METTL3 complex promotes cell proliferation, invasion and EGFR/AKT signaling in cervical cancer

Authors:
- Chao Zhang
- Xiang Fan
- Jia Yang
- Pengfeng Zhu
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Affiliations: Department of Gynecology, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu 213000, P.R. China
Published online on: June 26, 2025 https://doi.org/10.3892/or.2025.8936
Article Number: 103
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Eukaryotic translation initiation factor 3B (EIF3B), a translation initiation factor, has been identified to directly interact with methyltransferase‑like (METTL) family members to regulate translation and oncogenic transformation in various types of cancers. However, the interaction mechanism of EIF3B with METTL3 has not yet been reported in cervical cancer (CC). The present study further investigated the interaction between EIF3B and METTL3, as well as their regulatory effect on the malignant behaviors of CC cells. EIF3B overexpression plasmid (oeEIF3B) or small interfering RNA (siRNA; siEIF3B) and negative controls (oeNC and siNC) were transfected into HeLa and SiHa cells. In addition, METTL3 siRNA (siMETTL3) and siNC were transfected along with oeEIF3B or oeNC into HeLa and SiHa cells. Co‑immunoprecipitation was performed to determine the interaction between EIF3B and METTL3. EIF3B expression was found to be elevated in CC cell lines (C‑33A, HeLa, SiHa and CaSki) compared with the control cell line. oeEIF3B accelerated the proliferation and invasion and attenuated the apoptosis of both HeLa and SiHa cells, while siEIF3B exerted an opposite effect. In addition, oeEIF3B activated the EGFR/AKT signaling pathway, whereas siEIF3B suppressed it. Of note, EIF3B and METTL3 formed a complex, according to co‑immunoprecipitation assay; moreover, EIF3B and METTL3 could not regulate the expression of each other. Regardless of the presence or absence of oeEIF3B, siMETTL3 suppressed cell proliferation and invasion, and inhibited EGFR/AKT signaling, while promoting the apoptosis of HeLa and SiHa cells. More importantly, oeEIF3B lost its effect on these cellular functions following the addition of siMETTL3, suggesting that the EIF3B‑METTL3 complex, but not EIF3B alone, plays a cancer‑promoting role in CC. On the whole, the present study demonstrates that the EIF3B‑METTL3 complex induces cell proliferation and invasion, and activates EGFR/AKT signaling in CC.

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