Long non-coding RNA NORAD exhaustion represses prostate cancer progression through inhibiting TRIP13 expression via competitively binding to miR-495-3p

Abstract

Abstract Background Prostate cancer (PCa) is a malignant heterogeneous tumor that threatens men’s health. Long non-coding RNA activated by DNA damage (NORAD) and microRNA-495-3p (miR-495-3p) have been revealed to be concerned with the tumorigenesis and progression of diverse cancers. Nevertheless, the regulatory mechanism between NORAD and miR-495-3p in PCa is unclear. Methods The expression of NORAD, miR-495-3p, and thyroid hormone receptor interactor 13 (TRIP13) mRNA was detected with quantitative real-time polymerase chain reaction (qRT-PCR). The levels of Bcl-2, Bax, Cleaved-casp-3, TRIP13, cyclin D1, and PCNA were detected through western blot analysis. The proliferation, apoptosis, migration, and invasion of PCa cells were assessed through 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), flow cytometry, or transwell assays. The relationship between NORAD or TRIP13 and miR-495-3p was confirmed via dual-luciferase reporter, RIP, or RNA pull-down assays. Results NORAD and TRIP13 were upregulated while miR-495-3p was downregulated in PCa tissues and cells. Both NORAD silencing and miR-495-3p upregulation accelerated cell apoptosis and curbed cell proliferation, migration, and invasion in PCa cells. Also, NORAD silencing repressed tumor growth in vivo. Notably, NORAD modulated TRIP13 expression by competitively binding to miR-495-3p. Furthermore, miR-495-3p repression reversed NORAD knockdown-mediated effects on the malignant behaviors of PCa cells. Moreover, TRIP13 enhancement overturned the effects of miR-495-3p overexpression on the proliferation, apoptosis, migration, and invasion of PCa cells. Conclusion NORAD depletion inhibited PCa advancement via the miR-495-3p/ TRIP13 axis, which provided a potential tactic for PCa treatment.