Abstract 2055: miR-17-3p suppresses tumorigencity of prostate cancer through inhibiting mitochondrial antioxidant enzymes

Abstract

Abstract Aberrant micro RNA (miRNA) expression has been implicated in pathogenesis of cancer. Recent studies have shown that miR-17-92 cluster is overexpressed in many types of cancer (Venturini et al Blood 2007; Mendell Cell 2008). The oncogenic function of mature miRNAs encoded by the miR17-92 cluster was identified from the 5’ arm of six precursor including miR-17, miR-18a, miR-19a, miR-20a, miR-19b-1, and miR-92-1. However, function of the miRNAs produced from the 3’ arm of these precursors remains to be elucidated. The present study demonstrates that miR-17-3p is able to suppress multiple primary mitochondrial antioxidant enzymes including manganese superoxide dismutase (MnSOD or SOD2), glutathione peroxidase-2 (GPX2), and thioredoxin reductase-2 (TXNRD2). Transfection of miR17-3p into prostate cancer PC-3 cells significantly reduced levels of the three antioxidant proteins and activity of the luciferase reporter under the control of identified miR-17-3p blinding sequences located in the 3’-untranslated regions of the three target genes. Disulfiram, a drug used to treat chronic alcoholism and also shown to have anticancer effect, induces the level of mature miR-17-3p and apoptotic cell death in PC-3 cells, which can be attenuated by transfection of antisense miR-17-3p. Increasing miR17-3p level in PC-3 cell by a Tet-on-based conditional expression system markedly suppressed its tumorigencity and enhanced its radiosensitivity. These results suggest that miR-17-3p may suppress aggressiveness of prostate cancer through inhibition of mitochondrial antioxidant enzymes. 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 2055.