Abstract 134: The regulatory role of microRNA 338-3p in malignant gliomas

Abstract

Introduction: Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. Even with optimal therapy, more than 70% of GBM patients will die within 2 years of diagnosis. MicroRNAs (miR) are important regulators of gene expression through posttranscriptional silencing of target mRNA. MicroRNA roles in cell proliferation, invasion, angiogenesis, and glioma stem cell activity are little known. In this study, we focus on the expression and function of microRNAs in human gliomas. Methods: Using RNA extracted from 15 GBM patient samples and serum collected from 2 glioma patients, miR 338-3p expression, relative to normal brain and control serum, was examined using RT PCR. Regional miR expression within a single tumor was identified. A DNA fragment containing the hsa-miR-338-3p locus was amplified and cloned into a lentiviral vector, then transduced into GBM neurosphere lines. MicroRNA 338-3p and its downstream target, expression was assessed by RT PCR and western blot. GBM neurosphere growth was examined in vitro. Results: Over-expression in miR 338-3p is associated with decreased glioma cell proliferation and neurosphere formation. MicroRNA 338-3p shows decreased expression in the core of malignant gliomas with increased expression at the tumors rim and migrating edge. MiR 338-3p expression induces cleaved caspase 3 expression. MiR 338-3p targets Histone deacetylase 4 (HDAC4). Conclusion: MicroRNA 338-3p inhibits GBM neurosphere growth in vitro through reducing proliferation and inducing apoptosis possibly via targeting of HDAC4. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 134. doi:10.1158/1538-7445.AM2011-134