title: A feed-forward regulatory loop between androgen receptor and PlncRNA-1 promotes prostate cancer progression.
abstract: 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.
authors.affiliation: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Ziyu
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Department of Spinal Surgery, Changzheng Hospital Affiliated to Second Military Medical University, 415th Feng Yang Road, Shanghai, 200003, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Yaoming
authors.initials: Y
authors.lastname: Li
authors.affiliation: Health Division of Guard Bureau, General Staff Department of Chinese People's Liberation Army, Beijing, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Shancheng
authors.initials: S
authors.lastname: Ren
authors.affiliation: Research Center of Developmental Biology, Second Military Medical University, 800th Xiangyin Road, Shanghai, 200433, China; Translational Medicine Center, Second Military Medical University, 800th Xiangyin Road, Shanghai, China.
authors.forename: Houqi
authors.initials: H
authors.lastname: Liu
authors.affiliation: Research Center of Developmental Biology, Second Military Medical University, 800th Xiangyin Road, Shanghai, 200433, China; Translational Medicine Center, Second Military Medical University, 800th Xiangyin Road, Shanghai, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Fubo
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Min
authors.initials: M
authors.lastname: Qu
authors.affiliation: Department of Pathology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Yasheng
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Yao
authors.affiliation: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Hou
authors.affiliation: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Chuanliang
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. Electronic address: sunyh@medmail.com.cn.
authors.forename: Yinghao
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D057809:HEK293 Cells; D064593:Heterografts; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D062085:RNA, Long Noncoding / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation
chemical_list: C410798:AR protein, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; C587820:PlncRNA-1, human; D062085:RNA, Long Noncoding; D011944:Receptors, Androgen
keywords: Androgen receptor; Long non-coding RNA; PlncRNA-1; Prostate cancer; microRNA