Involvement of microRNA-21 in mediating chemo-resistance to docetaxel in androgen-independent prostate cancer PC3 cells.
OBJECTIVE
To investigate whether microRNA-21 was involved in mediating the chemoresistance of prostate cancer cells to docetaxel.


METHODS
A microarray technique was used to determine the miRNA profile in docetaxel-resistant PC3 cells. Real-time PCR was used to confirm the array results. miR-21 mimics and inhibitors were synthesized and introduced to cells using Lipofectamine 2000. Cell proliferation was examined with the CCK-8 assay. Luciferase reporter containing PDCD 3'UTR was constructed and the activity was detected by a dual luciferase assay. PDCD4 protein expression was evaluated using Western blot.


RESULTS
A docetaxel-resistant prostate cancer PC3 cell line (PC3R) was established . Using microarrays, miR-21 was found to be up-regulated in PC3R cells. Ectopic expression of miR-21 increased the resistance to docetaxel in PC3 wild type cells. In contrast, silencing of miR-21 in PC3R cells sensitized the cells to docetaxel. The IC(50) values for miR-21-silencing cells and control cells were 28.31 and 35.89 nmol/L, respectively. PDCD4, a direct target gene of miR-21, could mediate chemoresistance to docetaxel in PC3 cells.


CONCLUSIONS
Our findings suggest that miR-21 contributed to the resistance of PC3 cells to docetaxel, and that targeting miR-21 may offer a promising therapeutic approach in sensitizing prostate cancer to docetaxel treatment.
Shi
Guo-hai
GH
Department of Urology, Cancer Hospital, Fudan University, Shanghai, China.
Ye
Ding-wei
DW
Yao
Xu-dong
XD
Zhang
Shi-ling
SL
Dai
Bo
B
Zhang
Hai-liang
HL
Shen
Yi-jun
YJ
Zhu
Yao
Y
Zhu
Yi-ping
YP
Xiao
Wen-jun
WJ
Ma
Chun-guang
CG
D000970:Antineoplastic Agents / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D020128:Inhibitory Concentration 50; D008055:Lipids; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D043823:Taxoids / Q000494:pharmacology*
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D008055:Lipids; C086724:Lipofectamine; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins; D043823:Taxoids; D000077143:Docetaxel