Abstract
Our recent studies of the microRNA (miRNA) expression signature in prostate cancer (PCa) indicated that miRNA-218 (miR-218) was significantly downregulated in clinical specimens, suggesting that miR-218 might act as a tumor-suppressive miRNA in PCa. The aim of the present study was to investigate the functional significance of miR-218 in PCa and to identify novel miR-218-regulated cancer pathways and target genes involved in PCa oncogenesis and metastasis. Restoration of miR-218 in PCa cell lines (PC3 and DU145) revealed that this miRNA significantly inhibited cancer cell migration and invasion. Gene expression data and in silico analysis demonstrated that LIM and SH3 protein 1 (LASP1) is a potential target of miR-218 regulation. LASP1 is a cytoskeletal scaffold protein that plays critical roles in cytoskeletal organization and cell migration. Luciferase reporter assays showed that miR-218 directly regulated expression of LASP1. Moreover, downregulating the LASP1 gene significantly inhibited cell migration and invasion in cancer cells, and the expression of LASP1 was upregulated in cancer tissues. We conclude that loss of tumor-suppressive miR-218 enhanced cancer cell migration and invasion in PCa through direct regulation of LASP1. Our data on pathways regulated by tumor-suppressive miR-218 provide new insight into the potential mechanisms of PCa oncogenesis and metastasis.