METTL3 mediates m6A methylation modification of ULBP2 and affects the progression of cervical cancer.

Background: Cervical cancer (CC) is one of the most prevalent malignancies in women, posing a significant challenge globally. However, the precise molecular mechanism regulating CC progression through methyltransferase-like protein 3 (METTL3) and UL16 Binding Protein 2 (ULBP2) remains largely unknown.

Methods: Bioinformatic analysis was used to identify the effect of ULBP2 expression in CC tissues. RT-qPCR and western blotting were employed to assess the mRNA and protein expression in CC cells and tissues. Methylthiazolyldiphenyl-tetrazolium bromide (MTT), 5‑Ethynyl‑2'‑deoxyuridine (EdU), wound healing, and transwell assays were utilized to estimate cell viability, proliferation, and metastasis, respectively. Cell apoptosis was detected by flow cytometry. CC cells were treated with different doses of radiotherapy. The m6A level was measured using methylated RNA immunoprecipitation (MeRIP) assay. A xenograft assay was conducted to further verify the roles of ULBP2 in CC.

Results: ULBP2 was upregulated in CC. Downregulation of ULBP2 restrained the proliferation, metastasis and radiotherapy resistance of CC cells. METTL3 regulated m6A methylation modification of ULBP2. Insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) promoted m6A methylation modification of ULBP2. METTL3 influenced the expression of ULBP2 and impacted the biological function of the CC cells. Silencing ULBP2 reduced the radioresistance of CC in vivo. Radiotherapy altered the gut microbiota in CC patients.

Conclusion: METTL3 modulated the m6A methylation of ULBP2, affecting the oncogenic properties and radioresistance of CC cells.