MiR-199a-3p Inhibits Aurora Kinase A and Attenuates Prostate Cancer Growth New Avenue for Prostate Cancer Treatment

被引:35
作者
Qu, Yi [1 ]
Huang, Xiang [2 ]
Li, Zhiqing [2 ]
Liu, Junyan [1 ]
Wu, Jinlin [1 ]
Chen, Dapeng [1 ]
Zhao, Fengyan [1 ]
Mu, Dezhi [1 ]
机构
[1] Sichuan Univ, Minist Educ, Key Lab Birth Defects, Chengdu 610041, Sichuan, Peoples R China
[2] Peoples Hosp Sichuan Prov, Dept Urol, Chengdu, Peoples R China
基金
中国国家自然科学基金;
关键词
SMALL-MOLECULE INHIBITOR; SUPPRESSES TUMOR-GROWTH; EXPRESSION; MICRORNAS; REGION;
D O I
10.1016/j.ajpath.2014.01.017
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Prostate cancer (PCa) is the most common solid tumor malignancy in men that severely influences quality of life. Surgery is most often the recommended treatment for PCa, but radical prostatectomy can cause significant urinary adverse effects. Therefore, finding effective biochemical treatments for PCa remains a necessity. Aurora kinase A has been shown to be involved in PCa progression, thus making it a good target for PCa therapy. miRNAs are important regulators of gene expression, with some miRNAs specifically involved in carcinogenesis. Therefore, herein, we identified miRNAs targeted to aurora kinase A and examined their effects on the growth of PCa. We used primary samples from PCa patients and PCa cell lines as research subjects. We demonstrate that miR-199a-3p is down-regulated in PCa tissues compared with normal prostate tissues, with the expression pattern inversely correlated with the expression pattern of aurora kinase A. We find that miR-199a-3p agomir inhibits aurora kinase A and attenuates xenograft tumor growth of PCa. Moreover, we demonstrate that down-regulation of miR-199a-3p results from enhancement of the methylation of miR-199a gene in PCa. Furthermore, we find that the expression level of miR-199a-3p is inversely correlated to tumor stage and Gleason score of PCa. Revealing novel mechanisms for oncogene inhibition by miRNA-mediated pathways offers new avenues for PCa treatment.
引用
收藏
页码:1541 / 1549
页数:9
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