Methyltransferase-like 14 promotes the tumorigenesis and proliferation of pancreatic cancer cells through myc proto-oncogene signaling pathway.

Abstract

Objective: Pancreatic cancer is characterized by low survival rate and rapid deterioration. Methyltransferase-like 14 (METTL14), as N6-methyladenosine (m6A) methyltransferase, is closely related to tumor progression. The purpose of this study is to look into how METTL14 affects pancreatic cancer tumorigenesis, cell division, and apoptosis.

Material and methods: We examined and contrasted the levels of METTL14 protein and messenger RNA expression in human pancreatic ductal cells and human pancreatic cancer cells. After silencing or upregulating METTL14, the proliferative ability, migration ability, and cell apoptosis of pancreatic tumor cells was detected by colony-forming assay, wound scratch healing assay, cell counting kit 8 assay, and terminal deoxynucleotidyl transferasemediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling assay. Following the use of c-Myc inhibitor (10058-F4), western blot analysis was carried out to investigate the key factor expression and c-Myc signaling pathway activation status.

Results: METTL14 was preferentially expressed in human pancreatic cancer cells PANC-1 and SW1990 than in human normal pancreatic duct cells human pancreatic nestin-expressing cells (HPNE) (P < 0.001). Overexpression of METTL14 increased the tumorigenic and proliferative ability of pancreatic cancer cells. Overexpression of METTL14 decreased apoptosis rate. Western blot assay showed that nucleus b-catenin increased when METTL14 was overexpressed, and nucleus b-catenin decreased when METTL14 was silenced in PANC-1 cell (P < 0.01). The protein expression of other key factors, such as c-Myc, matrix metalloproteinase (MMP)-9, and MMP-2, were also affected. The use of c-Myc inhibitor (10058-F4) on the basis of OE-METTL14 reversed the effect of the overexpression of METTL14 on promoting the tumorigenesis and cell proliferation of pancreatic cancer cell lines PANC-1 and SW1990.

Conclusion: METTL14 promoted the tumorigenesis and proliferation of pancreatic cancer cells by the c-Myc signaling pathway.