Abstract Prostate cancer remains one of the most prevalent cancers and a major cause of morbidity and mortality in the western world. Disease progression and the development of hormone refractory disease remain major causes of cancer-related death. The understanding of the new molecular pathways of hormone refractory would be helpful in improving diagnosis and therapy of the disease. microRNAs (miRNAs) are small, non-coding RNAs with a length of approximately 22 nucleotides. They regulate gene expression by promoting mRNA cleavage and at the posttranscriptional level by translational suppression. They play important roles in various biological and metabolic processes, including development, differentiation, signal transduction, cell maintenance, and cancer. Bioinformatic predictions indicate that miRNAs regulate more than 30% of the protein coding genes. It is estimated that approximately 1,000 miRNAs exist in the vertebrate genome. An important role for miRNAs in the development of cancer has emerged in recent years. miRNAs are aberrantly expressed in many human cancers, and they may function as oncogenes or tumor suppressors. Up-regulated miRNAs could function as oncogenes by negatively regulating tumor suppressor genes, while down-regulated miRNAs could act as tumor suppressors, inhibiting cancers by regulating oncogenes. Down-regulation of miR-145 has been reported in many types of human cancer, including prostate cancer, suggesting that miR-145 function as a tumor suppressor. In this study, we focused on target identification of miR-145 in prostate cancer, based on gene-wide gene expression analysis of miR-145 transfection cells. According to our expression analysis showed that down-regulated genes (FSCN1, UNG and EIF4EBP2) were identified. Loss-of-function assays revealed that FSCN1 inhibited cell proliferation, migration, and invasion in PC3 and DU145 cells, suggesting FSCN1 function as an oncogene. The identification of tumor suppressive miRNA and their target genes could provide new insights into potential mechanisms of prostate carcinogenesis. 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 123. doi:10.1158/1538-7445.AM2011-123