SIRT1 (Sirtuin 1) is the most well-known member of the class III histone deaceylase family which plays key roles in many cellular pathways by deacetylating or interacting with numerous non-histone proteins. Recent evidence has demonstrated that SIRT1 is up-regulated in a variety of human cancers and inhibition of SIRT1 expression or activity induces cancer cell growth retardation, cell cycle arrest and apoptosis. Although the functions of SIRT1 in cancer have been extensively studied, the underlying mechanisms of aberrant regulation of SIRT1 are not clearly understood. In the present study, we identified 5 microRNAs (miRNAs) that were significantly down-regulated in human hepatocellular carcinomas (HCCs) via large-scale miRNA expression analysis with computational prediction of miRNA targeting for SIRT1. Of these, it was found that miR-29c and miR-141 were directly able to suppress endogenous SIRT1 expression, but only miR-29c was able to recapitulate the effects of SIRT1 inactivation in HCC cells. In addition, the expression level of miR-29c was inversely correlated with SIRT1 protein expression levels in a subset of HCC tissues with their corresponding noncancerous tissue. The ectopic expressions of miR-29c in SNU-182 liver cancer cell lines suppressed cell growth and induced cell cycle arrest at G1-phase accompanied with the altered expressions of G1-related cellular components, such as CDK6, CDK2, cyclin D1, cyclin D3, phosphorylation of Rb and E2F1. Taken together, we suggest that loss or down-regulation of endogenous miR-29c causes aberrant overexpression of SIRT1 contributing oncogenic potential to the cells, and that a novel tumor suppression mechanism involving miR-29c may be amenable to epigenetic regulation in human HCC.

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 179. doi:1538-7445.AM2012-179

©2012 American Association for Cancer Research
2012