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

  • Authors:
    • Chao Zhang
    • Xiang Fan
    • Jia Yang
    • Pengfeng Zhu
  • View Affiliations / Copyright

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

Figure 1

Elevated EIF3B mRNA and protein
expression in cervical cancer cells vs. normal cervical epithelial
cells. (A) EIF3B mRNA expression in C-33A, HeLa, SiHa and CaSki
cell lines vs. HCerEpiC cells. (B and C) Western blot analysis of
EIF3B protein expression. (B) Representative western blots and (C)
quantification of EIF3B protein expression in C-33A, HeLa, SiHa and
CaSki cell lines vs. HCerEpiC cells. EIF3B, eukaryotic translation
initiation factor 3B; HCerEpiC, human cervical epithelial cells.
*P<0.05, **P<0.01 and ***P<0.001.

Figure 2

EIF3B promotes cell proliferation and
invasion, whereas it inhibits apoptosis in cervical cancer. (A)
Quantification of EIF3B mRNA expression among groups following
transfection in Hela and SiHa cell lines. (B) Representative
western blots and (C) quantification of EIF3B protein expression
among the groups following transfection in Hela and SiHa cell
lines. (D) Effect of EIF3B on HeLa and SiHa cell proliferative
capacity. (E) TUNEL assay. (F) Effect of EIF3B on HeLa and SiHa
cell apoptotic rate. (G) Transwell assay. (H) Effect of EIF3B on
HeLa and SiHa invasive cell count. EIF3B, eukaryotic translation
initiation factor 3B; si-, small interfering; oe-, overexpressing;
NC, negative control. *P<0.05, **P<0.01 and
***P<0.001.

Figure 3

EIF3B interacts with METTL3 and
activates EGFR/AKT signaling in cervical cancer cells. (A)
Representative western blots of co-immunoprecipitation assay. (B)
Effect of EIF3B on EGFR mRNA expression in HeLa and SiHa cell
lines. (C and D) Effects of EIF3B on EGFR protein and p-AKT
expression. (C) Representative western blots and (D) quantification
of EGFR protein and p-AKT expression in HeLa and SiHa cell lines.
EIF3B, eukaryotic translation initiation factor 3B; METTL3,
methyltransferase-like 3; p-, phosphorylated; si-, small
interfering; oe-, overexpressing; NC, negative control. *P<0.05,
**P<0.01 and ***P<0.001.

Figure 4

EIF3B directly binds to METTL3 in
cervical cancer cells. METTL3 and EIF3B mRNA expression
quantification among the groups following transfection in Hela and
SiHa cell lines (A). (B) Representative western blots and (C)
quantification of METTL3 and EIF3B protein expression among the
groups following transfection in Hela and SiHa cell lines. EIF3B,
eukaryotic translation initiation factor 3B; METTL3,
methyltransferase-like 3; si-, small interfering; oe-,
overexpressing; NC, negative control; ns, not significant.
*P<0.05, **P<0.01 and ***P<0.001.

Figure 5

EIF3B-METTL3 complex plays a cervical
cancer-promoting role. (A) Effect of the EIF3B-METTL3 complex on
HeLa and SiHa cell proliferative capacity, (B) cell apoptotic rate,
and (C) invasive cell count. (D) TUNEL assay and (E) Transwell
assay. EIF3B, eukaryotic translation initiation factor 3B; METTL3,
methyltransferase-like 3; si-, small interfering; oe-,
overexpressing; NC, negative control; ns, not significant.
*P<0.05, **P<0.01 and ***P<0.001.

Figure 6

EIF3B-METTL3 complex promotes
EGFR/AKT signaling in cervical cancer cells. (A) Effect of the
EIF3B-METTL3 complex on EGFR mRNA expression in HeLa and SiHa cell
lines. (B and C) Effect of EIF3B-METTL3 complex on EGFR protein and
p-AKT expression. (B) Representative western blots and (C)
quantification of EGFR protein and p-AKT expression in HeLa and
SiHa cell lines. EIF3B, eukaryotic translation initiation factor
3B; METTL3, methyltransferase-like 3; p-, phosphorylated; si-,
small interfering; oe-, overexpressing; NC, negative control; ns,
not significant. *P<0.05, **P<0.01 and ***P<0.001.

Figure 7

Schematic diagram of the EIF3B-METTL3
complex in cervical cancer. EIF3B, eukaryotic translation
initiation factor 3B; METTL3, methyltransferase-like 3.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang C, Fan X, Yang J and Zhu P: EIF3B‑METTL3 complex promotes cell proliferation, invasion and EGFR/AKT signaling in cervical cancer. Oncol Rep 54: 103, 2025.
APA
Zhang, C., Fan, X., Yang, J., & Zhu, P. (2025). EIF3B‑METTL3 complex promotes cell proliferation, invasion and EGFR/AKT signaling in cervical cancer. Oncology Reports, 54, 103. https://doi.org/10.3892/or.2025.8936
MLA
Zhang, C., Fan, X., Yang, J., Zhu, P."EIF3B‑METTL3 complex promotes cell proliferation, invasion and EGFR/AKT signaling in cervical cancer". Oncology Reports 54.3 (2025): 103.
Chicago
Zhang, C., Fan, X., Yang, J., Zhu, P."EIF3B‑METTL3 complex promotes cell proliferation, invasion and EGFR/AKT signaling in cervical cancer". Oncology Reports 54, no. 3 (2025): 103. https://doi.org/10.3892/or.2025.8936
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang C, Fan X, Yang J and Zhu P: EIF3B‑METTL3 complex promotes cell proliferation, invasion and EGFR/AKT signaling in cervical cancer. Oncol Rep 54: 103, 2025.
APA
Zhang, C., Fan, X., Yang, J., & Zhu, P. (2025). EIF3B‑METTL3 complex promotes cell proliferation, invasion and EGFR/AKT signaling in cervical cancer. Oncology Reports, 54, 103. https://doi.org/10.3892/or.2025.8936
MLA
Zhang, C., Fan, X., Yang, J., Zhu, P."EIF3B‑METTL3 complex promotes cell proliferation, invasion and EGFR/AKT signaling in cervical cancer". Oncology Reports 54.3 (2025): 103.
Chicago
Zhang, C., Fan, X., Yang, J., Zhu, P."EIF3B‑METTL3 complex promotes cell proliferation, invasion and EGFR/AKT signaling in cervical cancer". Oncology Reports 54, no. 3 (2025): 103. https://doi.org/10.3892/or.2025.8936
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