Long non-coding TUG1 accelerates prostate cancer progression through regulating miR-128-3p/YES1 axis.

Abstract

Dysregulation of long non-coding RNAs (lncRNAs) is being found to have relevance to human cancers, including prostate cancer (PCa). Taurine-upregulated gene 1 (TUG1) has been demonstrated to have a potential oncogenic role in PCa. Then the aim of this study was to investigate the molecular mechanisms of TUG1 on PCa progression. The expression levels of TUG1, YES proto-oncogene 1 (YES1) mRNA and miR-128-3p were assessed using quantitative real-time polymerase chain reaction. Cell proliferation ability, apoptosis, and migration and invasion capacities were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, flow cytometry and transwell assay, respectively. Western blot analysis was employed to evaluate the indicated proteins levels. The interaction between miR-128-3p and TUG1 or YES1 was determined using the Dual-Luciferase reporter assay. In vivo assay was used to observe the effect of TUG1 on tumor growth in vivo. Our data indicated that TUG1 was upregulated in PCa tissues and cells and predicted poor prognosis. TUG1 knockdown weakened PCa cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and accelerated cell apoptosis in vitro. Mechanistically, TUG1 directly interacted with miR-128-3p and miR-128-3p mediated the regulatory effects of TUG1 depletion on PCa cell progression. YES1 was a direct target of miR-128-3p and TUG1 modulated YES1 expression by sponging miR-128-3p. Moreover, TUG1 silencing repressed PCa cell progression in vitro through YES1. Additionally, TUG1 silencing mitigated tumor growth in vivo. Our study suggested that TUG1 silencing retarded PCa cell progression in vitro and tumor growth in vivo through miR-128-3p/YES1 axis, showing that targeting TUG1 might be a novel therapeutic strategy for PCa management.