Epigenetic Silencing of MicroRNA-375 Regulates PDK1 Expression in Esophageal Cancer

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-375 (miR-375) during tumorigenesis. Whether or not down-regulation of miR-375 also exists in esophageal cancer is unknown. Our aim was to test the hypothesis that down-regulation of miR-375 also exists in esophageal cancer. Expression of levels of miR-375 were examined using real-time PCR on paired esophageal cancer and adjacent non-cancerous tissues. The methylation status is detected by methylation specific-PCR (MSP). The results show that miR-375 is downregulated by hypermethylation of the promoter in esophageal cancer tissues. Epigenetic silencing of miR-375 induced an up-regulation of its targets, 3-phosphoinositide-dependent protein kinase-1 (PDK1). Restoration of the miR-375 expression in esophageal cancer cell lines downregulated the PDK1 expression. Furthermore, the miR-375 expression was found to be inversely correlated with PDK1 expression in esophageal cancer. Thus, miR-375 is frequently down-regulated in esophageal cancer and is a negative regulator of PDK1.