The UCA1/miR-204/Sirt1 axis modulates docetaxel sensitivity of prostate cancer cells.

Abstract

In this study, we firstly investigated the regulative effect of miR-204 on Sirt1 expression in prostate cancer cells. Then, we examined whether miR-204 downregulation in the cells is a result of UCA1 upregulation. In addition, the regulative effect of UCA1/miR-204/Sirt1 axis on docetaxel sensitivity of prostate cancer cells was studied. QRT-PCR was performed to detect UCA1, miR-204 and Sirt1 mRNA expression. Western blot assay was performed to assess Sirt1, P-gp and caspase-3 expression. The regulative effect of UCA1/miR-204/Sirt1 axis on docetaxel sensitivity of prostate cancer cells was examined by measurement of docetaxel IC50, dictation of cleaved caspase-3 and flow cytometric analysis of cell apoptosis. MiR-204 negatively modulated Sirt1 expression in prostate cancer cells. UCA1 upregulation directly resulted in decreased miR-204 expression. UCA1 overexpression resulted in increased Sirt1 expression in PNT2 cells, while knockdown of endogenous UCA1 led to decreased Sirt1 in LNCaP and 22RV1 cells. UCA1 siRNA, Sirt1 siRNA and miR-204 mimics could enhance docetaxel-induced activation of caspase-3 and cell apoptosis in 22RV1/DR cells. There is a UCA1/miR-204/Sirt1 axis in LNCaP and 22RV1 cells. The UCA1/miR-204/Sirt1 axis plays an important role in modulating in vitro docetaxel sensitivity of the prostate cancer cells.