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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
The Department of Urology, Tianjin Institute of Urology, The 2nd Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin, 300211, China.
Xu
X
Wang
Department of Cardiology, Chinese PLA General Hospital, No. 28 Fu-xing Road, Beijing, 100853, China. dryangb@aliyun.com.
Bo
B
Yang
The Department of Urology, Tianjin Institute of Urology, The 2nd Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin, 300211, China.
Baojing
B
Ma
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000187:drug effects; D045744:Cell Line, Tumor; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D062085:RNA, Long Noncoding / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D034741:RNA, Small Interfering; D056564:Sirtuin 1 / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D043823:Taxoids / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; C549404:MIRN204 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D043823:Taxoids; C515159:UCA1 RNA, human; D000077143:Docetaxel; C505407:CASP3 protein, human; D053148:Caspase 3; C447939:SIRT1 protein, human; D056564:Sirtuin 1
Docetaxel; Prostate cancer; Sirt1; UCA1; miR-204