The RNA m6A methyltransferase METTL3 promotes pancreatic cancer cell proliferation and invasion

Abstract

Epigenetic modifications are involved in carcinogenesis and METTL3 is involved in RNA methylation. This study aimed to explore the role of the RNA m6A methyltransferase METTL3 in pancreatic cancer cells. The m6A modification was analyzed in human pancreatic cancer and paracancerous specimens, as well as in the normal HPDE6-C7 pancreatic cell line and the MIA-PaCa-2 and BxPC-3 pancreatic cancer cell lines. Immunohistochemistry (IHC), western blotting, and RT-qPCR were used to detect the expression of METTL3. Cell lines were transfected with siRNAs against METLL3. Proliferation, invasion, and migration were examined. The functions of METTL3 were predicted by bioinformatics analysis. In the 40 patients included, high METTL3 expression was associated with high pathological stage (P = 0.02) and high N stage (P = 0.02). Survival was better in patients with low METTL3 expression compared with those with high MTTL3 expression (P < 0.01). METTL3 and CIITA expression levels were inversely correlated (r = −0.71, P < 0.01). RNA m6A content in tumor specimens was significantly higher than that in paracancerous specimens. METTL3 protein and mRNA levels were significantly higher in tumor specimens compared with paracancerous specimens, as well as in cancerous cell lines vs. normal cells. METTL3 knockdown in MIA PaCa-2 and BxPC-3 cells decreased RNA m6A modifications. Cell proliferation, invasion, and migration were decreased by METTL3 knockdown in cancerous cell lines. A total of 673 differentially expressed genes were identified by bioinformatics: 659 were upregulated and 14 were downregulated. In conclusion, METTL3 is probably involved in pancreatic carcinogenesis. It could eventually be a prognostic marker or a treatment target.