MiR-137 Modulates Human Gastric Cancer Cell Proliferation, Apoptosis, and Migration by Targeting EZH2

Abstract

Gastric cancer (GC) is a malignancy of the digestive tract with rapid progress, poor prognosis, and low survival rate. The aberrant expression of microRNA (miRNA) is closely related to the tumorigenesis and progression of GC. The purpose of this study was to investigate the effects of miR-137 on the proliferation, apoptosis, and migration of GC cells. Bioinformatics analysis revealed that EZH2 expression in GC based on The Cancer Genome Atlas (TCGA) dataset was dramatically increased, miR-137 expression was down-regulated, and miR-137 was remarkably negatively correlated with EZH2 in GC. Next, it was found that EZH2 expression was significantly increasing and miR-137 was significantly decreasing by quantitative polymerase chain reaction (qRT-PCR) in GC clinical specimens. In addition, miR-137 expression in GC cell lines was significantly lower than that in normal gastric parietal cells. TargetScan and star-Base were employed to predict that EZH2 was a potential target of miR-137, and subsequent luciferase reports confirmed this prediction. Western blot assay demonstrated that up-regulation of miR-137 decreased EZH2 expression in BGC-823 cells, whereas silenced miR-137 enhanced EZH2 expression in SGC-7901 cells. The gain/loss-of-function indicates that miR-137 regulates the proliferation, apoptosis, migration and epithelial-mesenchymal transition of GC cells. In conclusion, our findings indicate that miR-137 restrains migration and proliferation and induces apoptosis partially through negatively regulating the expression of EZH2 in GC cells.