IDDF2019-ABS-0235 METTL3 as a potential cancer prognostic marker promotes the proliferation and metastasis of gastric cancer cells

Background Gastric cancer serves as the fifth leading cause of malignancies, whose main cause of death is distant metastasis. Methyltransferase-like 3 (METTL3), a major component of N6-methyladenosine (m6A) methyltransferase complex, has been suggested to function as an oncogene in several cancers. However, its clinical value and biological mechanism in gastric cancer remain unknown. Therefore, we attempted to investigate the expression profiles, prognostic value and possible downstream signal pathways of METTL3 in gastric cancer in this study. Methods By analyzing data from the cancer genome atlas (TCGA), we depicted METTL3 expression profile and its possible downstream signal pathways in gastric cancer. Then, we further explored METTL3 expression and its prognostic values in 196 gastric cancers in our hospital. We established stable knockdown or overexpression of METTL3 gastric cancer SGC7901 cell lines to conduct in vitro and in vivo experiments. Results METTL3 was significantly elevated in tumor tissues relative to normal gastric mucosa at both mRNA and protein levels. Moreover, the results from Kaplan-Meier survival curves analysis and multivariate Cox regression analysis demonstrated that METTL3 serves as an independent prognostic factor for gastric cancer patients. Furthermore, METTL3 can promote cell proliferation, colony formation, and cell migration and invasion. Additionally, the results of gene set enrichment analysis (GSEA) indicated that the potential downstream pathways of METTL3 were involved in cell cycle controlling. The top four pathways were as follows: the DNA repair pathway, the mitotic spindle pathway, the G2M checkpoint pathway and the E2F targets pathway. Conclusions METTL3 was upregulated in gastric cancer and served as a promising prognostic biomarker for patients suffered this deadly disease. Moreover, METTL3 might play an oncogenic role in gastric cancer by the promotion of proliferation and invasion. The possible downstream pathways of METTL3 may be related to cell cycle controlling.