1. ¹Department of Urology, Veterans Affairs Medical Center and University of California, San Francisco, CA, USA
2. ²Department of Urology, University of California San Francisco School of Medicine, San Francisco, CA, USA
3. ³Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA

Correspondence: Dr EJ Noonan, Department of Urology, Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA. E-mail: emily.noonan@gmail.com; Professor R Dahiya, Urology Research Center, University of California San Francisco School of Medicine, 4150 Clement Street, San Francisco, CA 94121, USA. E-mail: Rdahiya@urology.ucsf.edu

Received 5 August 2008; Revised 1 December 2008; Accepted 14 December 2008; Published online 2 March 2009.

Abstract

Histone deacetylases (HDACs) are frequently overexpressed in broad range of cancer types, where they alter cellular epigenetic programming to promote cell proliferation and survival. However, the mechanism by which HDACs become overexpressed in human cancers remains somewhat of a mystery. In this study, we investigated the expression and functional significance of miR-449a in prostate cancer cells. Using real-time PCR, we found that miR-449a is downregulated in prostate cancer tissues relative to patient-matched control tissue. Introduction of miR-449a into PC-3 prostate cancer cells resulted in cell-cycle arrest, apoptosis and a senescent-like phenotype. In silico analysis of 3'-UTR regions identified a number of genes involved in cell-cycle regulation as putative targets of miR-449a. Using a luciferase 3'-UTR reporter system, we established that HDAC-1 (histone deacetylase 1), a gene that is frequently overexpressed in many types of cancer, is a direct target of miR-449a. Further, our data indicate that miR-449a regulates cell growth and viability in part by repressing the expression of HDAC-1 in prostate cancer cells. Our findings provide new insight into the function of miRNA in regulating HDAC expression in normal versus cancerous tissue.