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. 2011 Oct;56(10):2849-56.
doi: 10.1007/s10620-011-1711-1. Epub 2011 Apr 30.

Epigenetic silencing of microRNA-375 regulates PDK1 expression in esophageal cancer

Xiaoli Li  1 , Rui Lin, Jiansheng Li
Affiliations

Epigenetic silencing of microRNA-375 regulates PDK1 expression in esophageal cancer

Xiaoli Li et al. Dig Dis Sci. 2011 Oct.

Abstract

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.

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