Abstract 3968: MicroRNA-34a inhibits proliferation and invasion by targeting c-Myc in prostate cancer cells

Abstract

Abstract MicroRNA-34a (miR-34a), a potent p53 mediator, has been reported to function as a tumor suppressor. The proto-oncogene c-Myc regulates cell proliferation and transformation both transcriptionally and non-transcriptionally and is frequently deregulated in human cancers. Rho GTPases are small G proteins that regulate various cellular processes, including cytoskeletal dynamics, migration, cell proliferation, apoptosis, and transcription. RhoA has been shown to control cancer metastasis and progression and cross-talk between RhoA and c-Myc has been reported. We studied the functional effects of miR-34a on c-Myc and RhoA in PC-3 prostate cancer cells. Transfection of miR-34a into PC-3 cells strongly inhibited in vitro cell proliferation, in vivo xenograft growth and cell invasion and promoted apoptosis. miR-34a downregulated expression of c-Myc by targeting its 3’ UTR as shown by luciferase reporter assays. miR-34a was also found to repress RhoA expression. Overexpression of c-Myc reversed miR-34a suppression of RhoA expression and invasion, suggesting that miR-34a inhibits invasion by suppressing RhoA through c-Myc. We also found that miR-34a downregulated guanine nucleotide exchange factors (GEFs) which convert inactive GTPases to an active form. Our results demonstrate that miR-34a suppresses malignancy by targeting c-Myc in PC-3 prostate cancer cells. 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 3968. doi:10.1158/1538-7445.AM2011-3968