miR-137 Is Frequently Down-Regulated in Gastric Cancer and Is a Negative Regulator of Cdc42

MicroRNAs (miRNAs) are a class of small (19-25 nucleotides) noncoding RNAs that regulate the expressions of a wide variety of genes, including some involved in cancer development. Some recent studies show that DNA methylation contributes to down-regulation of microRNA-137 (miR-137) during tumorigenesis. Whether down-regulation of miR-137 also exists in gastric cancer is unknown. Our aim was to test the hypothesis that down-regulation of miR-137 also exists in gastric cancer. Expression of levels of miR-137 were examined using real-time PCR on paired gastric cancer and adjacent non-cancerous tissues. The methylation status is detected by MSP. Results show that miR-137 is downregulated by hypermethylation of the promoter in gastric cancer tissues. Epigenetic silencing of miR-137 induced an up-regulation of its targets, Cdc42. Restoration of the miR-137 expression in gastric cancer cell lines downregulated the Cdc42 expression. Restoration of the miR-137 and inactivation of Cdc42 induce apoptosis and cell cycle G1 arrest in gastric cancer cells. Furthermore, the miR-137 expression was found to be inversely correlated with CDC42 expression in gastric caner. miR-137 is frequently down-regulated in gastric cancer and is a negative regulator of Cdc42.