Abstract 5290: MicroRNA-495-3p functions as tumor suppressor by targeting multiple oncogenic epigenetic effector molecules in gastric cancer.

Abstract

Abstract Epigenetic effector molecules are involved in many biological processes by regulating post-translational histone modification and DNA methylation. Recent evidence has suggested that several epigenetic effectors are aberrantly over-expressed in gastric cancer (GC). However, underlying regulatory mechanisms of those molecules are not completely understood. In this study, we identified miR-495-3p which regulates multiple epigenetic effectors through a comprehensive miRNA profiling analysis with in silico target prediction in GC. The down-regulation of miR-495-3p was demonstrated in a subset of GC tissue, revealing inverse correlation with expression levels of epigenetic effectors that were predicted to be targeted by miR-495-3p. Ectopic overexpression of miR-495-3p in GC cells suppressed protein expression and 3’-UTR (untranslated region) reporter luciferase activity of multiple epigenetic effectors including histone deacetylase 2 (HDAC2), SET and MYND domain-containing protein 3 (SMYD3), DNA methyltransferase 1 (DNMT1) and metastasis-associated protein1 (MTA1). Moreover, miR-495-3p attenuated cancer cell proliferation accompanied with LC3B-II conversion, PARP cleavage, p16INK4A expression and down-regulation of CDK4/6 and cyclin D1, which were implicated in autophagic cell death, apoptosis and cell cycle regulation, respectively. In addition, ectopically over-expressed miR-495-3p inhibits cell migration via suppressing epithelial-mesenchymal transition (EMT)-related molecules, Snail and SLUG. Taken together, we suggest that a loss or down-regulation of endogenous miR-495-3p triggers aberrant overexpression of multiple oncogenic epigenetic effector molecules, and thereby miR-495-3p functions as a tumor suppressor in gastric tumorigenesis. Citation Format: Min Gyu Kim, Seung Jin Kim, Hyun Jin Bae, Ji Heon Noh, Jeong Kyu Kim, Jung Woo Eun, Kwang Hwa Jung, Young Gyoon Chang, Qingyu Shen, Won Sang Park, Jung Young Lee, Suk Woo Nam. MicroRNA-495-3p functions as tumor suppressor by targeting multiple oncogenic epigenetic effector molecules in gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5290. doi:10.1158/1538-7445.AM2013-5290 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.