MP41-17 MODIFIED 2005 ISUP GRADING IS ASSOCIATED WITH SIGNIFICANT UPGRADE AND BETTER PREDICTS METASTASIS

Abstract

are still unclear. Our miRNA expression signature of prostate cancer (PCa) showed that miR-23b/27b/24-1 clustered miRNAs were significantly downregulated in PCa. The aim of the present study was to investigate the functional significance of the miR-23b/27b/24-1 cluster and to identify the molecular targets regulated by this cluster in PCa cells. METHODS: Gain-of-function studies using mature miRNAs were performed to investigate cell proliferation, migration and invasion in PCa cell lines. To identify the molecular targets potentially regulated by the miR-23b/27b/24-1 cluster, we applied gene expression data and in silico analysis using TargetScan database [http://www.targetscan. org/] and GENECODIS software. Loss-of-function assays were performed to investigate the functional significance of miR-23b/27b/24-1 cluster target genes. RESULTS: Restoration of miR-23b, miR-27b and miR-24-1 in PCa cell lines revealed that these miRNAs significantly inhibited cancer cell migration and invasion. Gene expression data and in silico analysis demonstrated that golgi membrane protein 1 (GOLM1) was regulated by these clustered miRNAs. Silencing of the target gene resulted in significant inhibition of cell proliferation, migration and invasion in PCa cells. CONCLUSIONS: The miR-23b/27b/24-1 clusterd miRNAs were frequently down-regulated and function as tumor suppressors in PCa. Elucidation of the molecular targets regulated by the tumorsuppressive clustered miRNAs will provide new insights into the potential molecular mechanisms of PCa oncogenesis and metastasis and will facilitate the development of novel therapeutic strategies for the treatment of PCa.