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Erschienen in:
01.10.2011 | Original Article
Epigenetic Silencing of MicroRNA-375 Regulates PDK1 Expression in Esophageal Cancer
Erschienen in: Digestive Diseases and Sciences | Ausgabe 10/2011
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Background
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.
Aim
Our aim was to test the hypothesis that down-regulation of miR-375 also exists in esophageal cancer.
Methods
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).
Results
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.
Conclusion
Thus, miR-375 is frequently down-regulated in esophageal cancer and is a negative regulator of PDK1.