METTL3 Regulates the Translation of Oncogene Myc through m6A Modification and Promotes the Occurrence and Development of Cervical Cancer

Background: Cervical cancer (CC) is one of the major types of gynecological cancer, with a high global incidence and mortality rate. Methyltransferase-like 3 (METTL3), a key constituent of methyltransferase, plays a crucial role in various biological processes. Still, only a rare report has been made on its involvement in the progression of CC. Therefore, this study aims to investigate the impact of METTL3 in CC and its molecular mechanisms. Methods: Gene expression datasets about CC were obtained from the Gene Expression Omnibus (GEO) database, and the expression of METTL3 and Myc was analyzed. Cell viability was detected after METTL3 knockdown in HeLa and SiHa cells, followed by cell counting Kit-8 (CCK-8) assays. The relative expression of METTL3 and Myc was detected via real-time quantitative PCR (qPCR) assays, and the protein expression was determined using Western blot. Meanwhile, cell invasion and migration capabilities were assessed utilizing transwell assays, and cell proliferation was detected using the EdU experiment. Furthermore, RNA methylation immunoprecipitation-qPCR detection was performed to determine the expression of Myc after N-6-methyladenosine (m(6)A) modification. Results: Analysis of the GEO database indicated elevated expression of METTL3 and Myc in CC tissues. Patients with high METTL3 expression had shorter disease-free survival, and patients with high Myc expression had shorter overall survival. Following the knockdown of METTL3, there was a significant reduction in the viability, proliferation, invasion, and migration abilities of HeLa and SiHa cells. Besides, the expression of METTL3 and Myc mRNAs and proteins was greatly reduced. The level of m(6)A Myc decreased significantly after METTL3 knockdown. Conclusions: METTL3 plays an important role in regulating cervical cancer cells. METTL3 promotes CC development through m(6)A modification to regulate the expression of the oncogene Myc.