TUG1 knockdown inhibits the tumorigenesis and progression of prostate cancer by regulating microRNA-496/Wnt/β-catenin pathway

Our study aimed to further investigate the roles and molecular mechanisms of lncRNA taurine upregulated gene 1 (TUG1) in the development and progression of PC. RT-qPCR assay was carried out to measure expression of TUG1, miR-496, together with beta-catenin, cyclin D1 and c-myc. Protein levels of beta-catenin, cyclin D1 and c-myc were detected by western blot assay. Cell proliferative ability was assessed by colony formation assay and CCK-8 assay. Cell migratory and invasive capacities were evaluated by Transwell migration and invasion assay. The interaction between miR-496 and TUG1 was explored by bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation assay. Mouse xenograft experiments were performed to further investigate the roles and molecular basis of TUG1 in the tumorigenesis of PC in vivo. TUG1 was highly expressed in PC tissues and cells (DU145 and PC3). TUG1 knockdown inhibited proliferation, migration and invasion in DU145 and PC3 cells. Moreover, TUG1 suppressed miR-496 expression by direct interaction. TUG1 overexpression abrogated miR-96-mediated antiproliferation, anti-migration and anti-invasion effects in DU145 and PC3 cells. TUG1 knockdown inactivated Wnt/beta-catenin signaling pathway by upregulating miR-496 in DU145 and PC3 cells. Additionally, TUG1 knockdown inhibited DU145 cells derived PC xenograft growth by upregulating miR-496 and inactivating Wnt/beta-catenin signaling in vivo. TUG1 knockdown suppressed PC cell proliferation, migration and invasion in vitro and curbed PC xenograft growth in vivo by regulating miR-496/Wnt/ beta-catenin signaling pathway, deepening our understanding on etiology of PC.