We previously reported that PlncRNA-1, a long non-coding RNA that is up-regulated in prostate cancer (Pca), affects the proliferation and apoptosis of PCa cells. However, the molecular mechanisms underlying these effects remain largely unknown.
In this study, we demonstrated that long non-coding RNA PlncRNA-1, whose expression is promoted by Androgen Receptor (AR), protects AR from microRNA-mediated suppression in PCa cells. PlncRNA-1 knockdown resulted in the up-regulation of a series of AR-targeting microRNAs, among which miR-34c and miR-297 were found to regulate both AR and PlncRNA-1 expression at the post-transcriptional level. Functional analysis revealed that miR-34c and miR-297 overexpression down-regulated AR expression and inhibited the expression of downstream AR targets and that PlncRNA-1 overexpression rescued these effects. The association of PlncRNA-1 with tumor progression was also evaluated in mouse xenograft models, PCa tissues (16 paired samples), and blood samples (35 biopsy-negative and 37 biopsy-positive). Together, the data generated in this study indicate that PlncRNA-1 sponges AR-targeting microRNAs to protect AR from microRNA-mediated down-regulation and that these events form a regulatory feed-forward loop in the development of PCa. These findings suggest that PlncRNA-1 might potentially serve as a novel biomarker in PCa and that PlncRNA-1 might warrant further investigation to determine its potential role as a promising therapeutic target in PCa.
Cancer letters. 2016 Jan 22 [Epub ahead of print]
Ziyu Fang, Chen Xu, Yaoming Li, Xiaobing Cai, Shancheng Ren, Houqi Liu, Yue Wang, Fubo Wang, Rui Chen, Min Qu, Yang Wang, Yasheng Zhu, Wei Zhang, Xiaolei Shi, Jingjing Yao, Xu Gao, Jianguo Hou, Chuanliang Xu, Yinghao Sun
Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. , Department of Spinal Surgery, Changzheng Hospital Affiliated to Second Military Medical University, 415th Feng Yang Road, Shanghai, 200003, China. , Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. , Health Division of Guard Bureau, General Staff Department of Chinese People's Liberation Army, Beijing, P. R. China. , Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. , Research Center of Developmental Biology, Second Military Medical University, 800th Xiangyin Road, Shanghai, 200433, PR China; Translational Medicine Center, Second Military Medical University, 800th Xiangyin Road, Shanghai, 200433, PR China. , Research Center of Developmental Biology, Second Military Medical University, 800th Xiangyin Road, Shanghai, 200433, PR China; Translational Medicine Center, Second Military Medical University, 800th Xiangyin Road, Shanghai, 200433, PR China. , Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. , Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. , Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. , Department of Pathology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. , Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. , Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. , Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. , Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. , Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. , Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. , Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. , Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.