miR-128 modulates chemosensitivity and invasion of prostate cancer cells through targeting ZEB1.
OBJECTIVE
Recent reports strongly suggest the profound role of miRNAs in cancer therapeutic response and progression, including invasion and metastasis. The sensitivity to therapy and invasion is the major obstacle for successful treatment in prostate cancer. We aimed to investigate the regulative effect of miR-128/zinc-finger E-box-binding homeobox 1 axis on prostate cancer cell chemosensitivity and invasion.


METHODS
The miR-128 expression pattern of prostate cancer cell lines and tissues was detected by real-time reverse transcriptase-polymerase chain reaction, while the mRNA and protein expression levels of zinc-finger E-box-binding homeobox 1 were measured by real-time reverse transcriptase-polymerase chain reaction and western blot assay, respectively. Dual-luciferase reporter gene assay was used to find the direct target of miR-128. Furthermore, prostate cancer cells were treated with miR-128 mimic or zinc-finger E-box-binding homeobox 1-siRNA, and then the cells' chemosensitivity and invasion were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and transwell assay, respectively.


RESULTS
We found miR-128 expression obviously decreased in prostate cancer tissues compared with paired normal tissues. Restored miR-128 expression sensitized prostate cancer cells to cisplatin and inhibited the invasion. Furthermore, there was an inverse expression pattern between miR-128 and zinc-finger E-box-binding homeobox 1 in prostate cancer cells and tissues, and zinc-finger E-box-binding homeobox 1 was identified as a direct target of miR-128 in prostate cancer. Knockdown of zinc-finger E-box-binding homeobox 1 expression efficiently sensitized prostate cancer cells to cisplatin and inhibited the invasion. However, ectopic zinc-finger E-box-binding homeobox 1 expression impaired the effects of miR-128 on chemosensitivity and invasion in prostate cancer cells.


CONCLUSIONS
miR-128 functions as a potential cancer suppressor in prostate cancer progression and rational therapeutic strategies for prostate cancer would be developed based on miR-128/zinc-finger E-box-binding homeobox 1 axis.
Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei.
Xianglun
X
Sun
Jingzhou Central Hospital, Huazhong University of Science and Technology, Jingzhou, Hubei.
Youkong
Y
Li
Jingzhou Central Hospital, Huazhong University of Science and Technology, Jingzhou, Hubei.
Jie
J
Yu
Jingzhou Central Hospital, Huazhong University of Science and Technology, Jingzhou, Hubei.
Hong
H
Pei
Huangshi Central Hospital, Hubei Polytechnic University, Huangshi, Hubei, PR China.
Pengcheng
P
Luo
Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei Huangshi Central Hospital, Hubei Polytechnic University, Huangshi, Hubei, PR China zhangjie1231994@126.com.
Jie
J
Zhang
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D004396:Coloring Agents; D018450:Disease Progression; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles; D046509:Tissue Culture Techniques; D014157:Transcription Factors / Q000378:metabolism*; D000071799:Zinc Finger E-box-Binding Homeobox 1; D016335:Zinc Fingers / Q000187:drug effects
D000970:Antineoplastic Agents; D004396:Coloring Agents; D018398:Homeodomain Proteins; C545189:MIRN128 microRNA, human; D035683:MicroRNAs; D013778:Tetrazolium Salts; D013844:Thiazoles; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; C022616:thiazolyl blue
ZEB1; chemosensitivity; invasion; miR-128