LncRNA TUG1 Regulates The Malignant Biological Behavior Of Prostate Cancer Cells Through The NRF2 Signaling Pathway

Objective: Long noncoding RNAs(lncRNAs)have been identified to modulate the development and progression of prostate cancer(PCa)via the regulation of their target genes.However,the biological function underlying the effect of lncRNA TUG1 in PCa remains unclear.Therefore,we investigate the effect of TUG1 on the biological behavior of prostate cancer cells and its potential molecular mechanism.Methods: Reverse transcription-quantitative polymerase chain reaction(qRT-PCR)and Western blotting analysis were used to assess the mRNA expression of TUG1 and protein expression levels of Nrf2 pathway members,respectively.The migration,invasion,and proliferation abilities of cells were assessed by the wound-healing,Transwell migration/invasion,and CCK8 assays,respectively.Results: TUG1 was strikingly upregulated in PCa cells compared with non-tumorigenic human prostate epithelial cells.The LncTar Web Server,which is a bioinformatics tool,was used to predict the target association between TUG1 and Nrf2.Moreover,the expression of TUG1 showed astrikingly positive correlation with that of Nrf2 in TCGA PCa RNA-Seq data(r = 0.26,P = 4.63E-09).Subsequently,inhibition of TUG1 using siRNA resulted in deceased proliferation,migration,and invasion of PCa cells;however,these effects were reversed by treatment with oltipraz(an activator of Nrf2).Finally,we evaluated the Nrf2 pathway to reveal the underlying mechanism of TUG1 in PCa cells,and found that TUG1 knockdown decreased the protein expression of Nrf2 downstream members(e.g.,HO-1,FTH1,and NQO1).TUG1 knockdown inhibited the expression of the mesenchymal marker protein vimentin and promoted the expression of epithelial marker protein E-cadherin,oltipraz treatment can reverse this phenomenon.Conclusions: LncRNA TUG1 plays an oncogenic role in human PCa cells by promoting the cell proliferation and invasion in PCa cell lines,at least partly via the Nrf2 signaling pathway and participates in the biological process of epithelial-mesenchymal transformation.