PTEN is one of the most commonly lost tumor suppressors in human cancers. Deletion of PTEN in mice has been shown to induce steatohepatitis and the development of primary liver cancers (hepatocellular carcinoma and cholangiocarcinoma). This study provides novel evidence for epigenetic regulation of PTEN in both hepatocellular carcinoma and cholagniocarcinoma cells. Treatment of the hepatocellular carcinoma cell line (Huh-7) and cholangiocarcinoma cells line (TFK-1) with the DNA methyltransferase (DNMT) inhibitor, Decitabine (1 mM), and the histone deacetylase inhibitor, Trichostatin A (TSA, 10mM), increased the expression of PTEN protein. Methylation specific qPCR assay shows that Decitabine/TSA treatment significantly reduced the methylation of the CpG islands located at the PTEN gene promoter. Furthermore, we have shown that miR-185 and miR-200b target DNMT-1 and -3A/3B, respectively, thus upregulating the expression of PTEN in hepatic cancer cells. Forced overexpression of miR-185 or treatment with mimic miR-185 abolished the expression of DNMT1 protein and enhanced the level of PTEN protein in both Huh-7 and TFK-1 cells. Accordingly, miR-200b overexpression or mimic treatment significantly decreased DNMT3A and DNMT3B protein levels and enhanced the expression of PTEN. These results demonstrate a novel epigenetic regulation of PTEN by miR-185 and -200b which is critical in hepatic carcinogenesis

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3143. doi:1538-7445.AM2012-3143