Methyltransferase-like 3 (METTL3) has been identified as a methyltransferase responsible for N6-methyla-denosine (m6A) modification of mRNA. METTL3 functions in tumorigenesis and tumor development by promoting the translation of oncoproteins; however, the role of METTL3 in ovarian cancer has not been extensively studied. The present study performed immunohistochemistry to detect METTL3 expression levels in 52 samples of ovarian cancer tissue paired with corresponding paracancerous tissue. RNA interference was conducted to downregulate the expression levels of METTL3 in the SKOV3 and OVCAR3 ovarian cancer cell lines. Reverse transcription-quantitative PCR and western blot analysis demonstrated the effects of METTL3 knockdown on mRNA and protein levels, respectively. CCK-8, colony formation, apoptosis and Transwell assays were also performed. The results demonstrated that METTL3 exhibited significantly higher expression levels in ovarian cancer tissues compared with corresponding paracancerous tissue. High METTL3 expression levels were associated with large tumors, lymph node metastasis and high pathological grade. Cell proliferation analysis revealed that METTL3 knockdown reduced the proliferation and clonogenic ability of SKOV3 and OVCAR3 cells. Apoptotic rates were increased in METTL3-silenced ovarian cancer cells, which may have been mediated by the activation of the mitochondrial apoptosis pathway, and METTL3 knockdown reduced cell invasion. METTL3 knockdown downregulated the phosphorylation levels of AKT and the expression of the downstream effector Cyclin D1. These results suggested that METTL3 may serve an oncogenic function in the progression of human ovarian cancer cells partially through the AKT signaling pathway, indicating that METTL3 may be a potentially novel therapeutic target for the treatment of ovarian cancer.
Keywords: AKT; METTL3; apoptosis; mitochondria pathway; oncogene.
Copyright: © Liang et al.