Abstract 1915: microRNA-320a inhibits cancer cell migration and invasion through targeting LAMP1 in castration-resistant prostate cancer

Abstract

Abstract BACKGROUND: In early-stage prostate cancer (PCa), more than 90% of patients initially respond to the therapeutic use of androgen deprivation; however, many cases become refractory and progress to castration resistant prostate cancer (CRPC). CRPC is difficult to treat, and most clinical trials for advanced PCa with metastasis to bones or other sites have shown limited benefits. Therefore, understanding the molecular mechanisms of metastatic pathways of CRPC underlying current genomic approaches would help to improve therapies for this disease. Our recent studies of microRNA (miRNA) expression signatures of CRPC revealed that microRNA-320a (miR-320a) was significantly reduced in cancer tissues, suggesting miR-320a acts as a tumor-suppressor in CRPC cells. The aim of this study was to investigate the functional significance of miR-320a in CRPC cells and to identify miR-320a-mediated target genes involved in oncogenesis and metastasis of the disease. METHODS: Gain-of-function studies were performed using transfection of mature miR-320a into cancer cells (DU145 and PC3). Genome-wide gene expression analysis and in silico analysis were applied to identify molecular targets regulated by miR-320a in PCa cells. A luciferase reporter assay was carried out to determine regulation of miR-320a. Loss-of-function studies using siRNA were performed to investigate the functional role of target genes. RESULTS: The expression levels of miR-320a were significantly reduced in PCa tissues and the cell lines. Restoration of mature miR-320a in cancer cells led to significant inhibition of cell migration and invasion activities in PCa cell lines. Lysosomal-associated membrane protein 1 (LAMP1) was identified as a direct target of miR-320a in this assays. Silencing of LAMP1 significantly inhibited cell proliferation, migration and invasion in PCa cells. Moreover, overexpression of LAMP1 was observed in PCa and CRPC clinical specimens. CONCLUSIONS: To the best of our knowledge, this is the first report demonstrating that tumor-suppressive miR-320a directly regulated LAMP1 in PCa cells. The identification of novel target gene regulated by tumor-suppressive miRNAs may lead to a better understanding of molecular mechanisms of CRPC metastatic pathways. Citation Format: Atsushi Okato, Yusuke Goto, Akira Kurozumi, Mayuko Kato, Ryosuke Matsushita, Satoko Kojima, Shinichi Sakamoto, Tomohiko Ichikawa, Naohiko Seki. microRNA-320a inhibits cancer cell migration and invasion through targeting LAMP1 in castration-resistant prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1915.