Knockdown of METTL14 inhibits the growth and invasion of cervical cancer

Background: Increasing evidence has revealed that N-6-methyladenosine (m(6)A) modification is implicated in multiple biological functions in mammals. Methyltransferase-like 14 (METTL14), an important component of m(6)A modification, has been reported to play important roles in the pathogenesis of acute myeloid leukaemia and hepatocellular carcinoma metastasis. However, its role in cervical cancer remains unclear. Methods: Expression of METTL14 was knocked down by shRNA-METTL14 interference in HPV-positive and HPV-negative cervical cancer cell lines SiHa and C33a. CCK8, colony formation, wound-healing, and Transwell assays were performed to evaluate the effects of METTL14 knockdown on the proliferation, migration and invasion abilities of SiHa and C33a cells. Flow cytometry analysis was utilized to detect cell cycle distribution, and the expression of related proteins was examined by western blot analysis. Results: Bioinformatics analysis demonstrated that up-regulation of METTL14 acted as an adverse prognostic factor for overall survival in cervical cancer patients. We demonstrated that down-regulation of METTL14 inhibited the proliferation, migration and invasion abilities of SiHa and C33a cells. Moreover, silencing METTL14 induced cell cycle arrest in cervical cancer cells. METTL14 knockdown suppressed the PI3K/Akt/mTOR signaling pathway by decreasing the phosphorylation of Akt and mTOR, and the expression of downstream apoptosis-related proteins was also impacted. Conclusions: In conclusion, these data suggest an important oncogenic role of METTL14 in the growth and invasion of both HPV-positive and HPV-negative cervical cancer cells.