Abstract 2034: Tumor suppressive activity of Smad3 by regulation of microRNAs in gastric cancer

Abstract

Abstract Loss of the tumor suppressive effect of transforming growth factor-β (TGF-β) has been commonly found at later stages in carcinogenic progression. It was recently found that Smad3 expression is lost in more than a third of cancers and the introduction of Smad3 into Smad3 null gastric cancer cell line restores TGF-β-mediated growth inhibitory and tumor suppressive activity. Interestingly, expression of Smad3 induced the expression of E-cadherin. Since there is accumulating evidence that microRNAs (miRNAs) regulate transcriptional repressors of E-cadherin such as ZEB1 and ZEB2, thus affecting the expression of E-cadherin, we aimed to compare miRNA profiles of Smad3-negative gastric cell line (SNU484-LPCX) and Smad3-overexpressed one (SNU484-Smad3). To investigate global changes of miRNA profiles associated with Smad3 restoration, we applied massively parallel sequencing (MPS) to miRNA profiling. Using this approach, we identified more than 150 known miRNAs, and at least 10 miRNAs including miR200 show statistical significance in expression between two cell lines. To further confirm these findings, we applied qRT-PCR analysis of selected miRNAs and mRNAs. Using Smad3 specific siRNAs, we also proved that Smad3 is involved in the E-cadherin expression through the regulation of specific miRNAs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2034.