title: Identification of novel AR-targeted microRNAs mediating androgen signalling through critical pathways to regulate cell viability in prostate cancer.
abstract: MicroRNAs (miRNAs) have been recognized as significantly involved in prostate cancer (PCa). Since androgen receptor (AR) plays a central role in PCa carcinogenesis and progression, it is imperative to systematically elucidate the causal association between AR and miRNAs, focusing on the molecular mechanisms by which miRNAs mediate AR signalling. In this study, we performed a series of time-course microarrays to observe the dynamic genome-wide expressions of mRNAs and miRNAs in parallel in hormone-sensitive prostate cancer LNCaP cells stimulated by androgen. Accordingly, we introduced Response Score to identify AR target miRNAs, as well as Modulation Score to identify miRNA target mRNAs. Based on theoretical identification and experimental validation, novel mechanisms addressing cell viability in PCa were unravelled for 3 miRNAs newly recognized as AR targets. (1) miR-19a is directly up-regulated by AR, and represses SUZ12, RAB13, SC4MOL, PSAP and ABCA1, respectively. (2) miR-27a is directly up-regulated by AR, and represses ABCA1 and PDS5B. (3) miR-133b is directly up-regulated by AR, and represses CDC2L5, PTPRK, RB1CC1, and CPNE3, respectively. Moreover, we found miR-133b is essential to PCa cell survival. Our study gives certain clues on miRNAs mediated AR signalling to cell viability by influencing critical pathways, especially by breaking through androgen's growth restriction effect on normal prostate tissue.
authors: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, China.
authors: Wenjuan
authors: W
authors: Mo
authors: Jiyuan
authors: J
authors: Zhang
authors: Xia
authors: X
authors: Li
authors: Delong
authors: D
authors: Meng
authors: Yun
authors: Y
authors: Gao
authors: Shu
authors: S
authors: Yang
authors: Xuechao
authors: X
authors: Wan
authors: Caihong
authors: C
authors: Zhou
authors: Fenghua
authors: F
authors: Guo
authors: Yan
authors: Y
authors: Huang
authors: Stefano
authors: S
authors: Amente
authors: Enrico V
authors: EV
authors: Avvedimento
authors: Yi
authors: Y
authors: Xie
authors: Yao
authors: Y
authors: Li
mesh_terms: D000465:Algorithms; D000728:Androgens / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D019091:Critical Pathways; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008962:Models, Theoretical; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D000728:Androgens; D035683:MicroRNAs; D011944:Receptors, Androgen