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Abstract
Abstract Prostate cancer is the most frequent cancer of men in Western countries and causes second most of the cancer-related deaths. In addition to genetic changes also epigenetic alterations and micro-RNAs (miRNAs) are important in prostate cancer development. Our group has previously shown that miR-193b is hypermethylated in 22Rv1 prostate cancer cell line and that it is putative tumor suppressor in prostate cancer. In melanoma and hepatocellular carcinoma, it has been shown that CCND1, encoding cyclin D1 protein, is among the target genes of miR-193b. The aim of this project was to study if CCND1 is a target of miR-193b in prostate cancer. According to qRT-PCR and microarray analyses, the expression of CCND1 and miR-193b were inversely correlated in prostate cancer cell lines (PC-3, VCaP, 22Rv1, LAPC4, DU145, LNCaP) and in LuCaP xenografts. Using a luciferase reporter gene assay in 22Rv1 cells, we showed that miR-193b targets CCND1 3′UTR. In 22Rv1 cells with low endogenous miR-193b expression, transient pre-miR-193b transfection reduced CCND1 mRNA levels and cyclin D1 and phospho-RB protein levels. By rescue experiment we confirmed that the downregulation of cyclin D1 and phospho-RB proteins is due to miR-193b. When prostate cancer cell lines were treated with cdk4/6 inhibitor, 22Rv1 and VCaP cells with low miR-193b and high CCND1 expression showed significant growth retardation. In contrast, the inhibitor did not have any effect on the growth of PC-3 and DU145 cells with high miR-193b and low CCND1 expression. Furthermore, immunohistochemical analysis of 337 specimens showed that cyclin D1 is expressed significantly higher in castration resistant compared to hormone-naïve prostate cancers. Therefore, we conclude that CCND1 is one of the miR-193b targets in prostate cancer. Citation Format: Kirsi M. Tuppurainen, Hanna E. Rauhala, Mauro Scaravilli, Robert L. Vessella, Tapio Visakorpi. CCND1 is a miR-193b target in prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5205. doi:10.1158/1538-7445.AM2014-5205
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