Abstract 2033: Regulatory role of miR-203 in prostate cancer

Abstract

Abstract MicroRNAs (miRNAs) constitute an evolutionarily conserved class of small non-coding RNAs that primarily regulate gene expression at the post-transcriptional level via sequence-specific interaction with the 3’-untranslated regions (UTRs) of cognate mRNA targets. It is being increasingly recognized that miRNAs play roles in the establishment and progression of human malignancies. Several recent studies have shown that microRNAs are significantly altered in prostate cancer. Here we explored the role of miR-203 in prostate cancer progression and metastasis. RT-PCR analysis of prostate carcinoma cell lines showed that miR-203 expression is attenuated in prostate cancer. This attenuation was validated by in situ hybridization analysis of miR-203 in clinical specimens. To evaluate the functional significance of miR-203, miR-203 was reintroduced in prostate cancer cell lines followed by functional assays. Overexpression of miR-203 in prostate cancer cell line leads to decreases in cell growth, clonability, invasiveness and migratory properties. miR-203 reexpression in prostate carcinoma cell line induces cell cycle arrest at the G0-G1 phase of the cell cycle with a concomitant alteration of cell cycle regulators such as p21, p27, cyclin E and cdk2. Also, miR-203 transfection leads to a significant increase in apoptosis in prostate cancer cells pointing to the pleiotropic roles of this miR in prostate cancer. Further, analysis of putative miR-203 targets showed that miR-203 regulates the expression of survivin, a small inhibitor of apoptosis (IAP) protein that plays a key role in prostate cancer progression. In conclusion, our data suggests a crucial tumor suppressive role for miR-203 in prostate cancer. 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 2033.