title: MiR-185 attenuates androgen receptor function in prostate cancer indirectly by targeting bromodomain containing 8 isoform 2, an androgen receptor co-activator.
abstract: OBJECTIVE
  Aberrant androgen receptor (AR) signaling functions are implicated in prostate cancer (PCa) pathogenesis. Here, we studied interactions between miR-185 and the bromodomain containing 8 isoform 2 (BRD8 ISO2) to investigate indirect mechanisms of miR-185 with respect to AR function through BRD8 ISO2 in PCa.
  
  
  METHODS
  Putative miRNA response element (MRE) of miR-185 in 3'-untranslated region (3'-UTR) of BRD8 ISO2 mRNA was predicted by software and confirmed using dual-luciferase assays and Ago2 immunoprecipitation. BRD8 and AR expression were determined by qRT-PCR and Western blot in PCa cells and tissues. MMTV-Fluc reporter plasmids and dual-luciferase assays were used to evaluate AR activity.
  
  
  RESULTS
  MRE prediction, dual-luciferase assays and Ago2 immunoprecipitation confirmed that miR-185 is capable of binding the 3'-UTR of BRD8 ISO2 mRNA. QRT-PCR and Western blot indicated that BRD8 ISO2 expression is decreased by miR-185 mimic transfection while increased by miR-185 inhibitor transfection. MMTV-Fluc reporter assays revealed that miR-185 can attenuate AR function by suppressing BRD8 ISO2. Additionally, Pearson's correlation analyses confirmed that BRD8 ISO2 mRNA expression is inversely correlated with miR-185 expression in clinical specimens.
  
  
  CONCLUSIONS
  In addition to suppression of AR expression, miR-185 can attenuate AR function indirectly by suppressing BRD8 ISO2. MiR-185 and BRD8 ISO2 may be possible therapeutic targets for PCa treatment.
authors.affiliation: Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Chen-Yi
authors.initials: CY
authors.lastname: Jiang
authors.affiliation: Department of Urology, Shanghai General Hospital Affiliated to Nanjing Medical University, Shanghai 200080, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ruan
authors.affiliation: Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Xiao-Hai
authors.initials: XH
authors.lastname: Wang
authors.affiliation: Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Yi-Feng
authors.initials: YF
authors.lastname: Jing
authors.affiliation: Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Institute of Urology, Shanghai Jiao Tong University, Shanghai 200080, China.
authors.forename: Bang-Min
authors.initials: BM
authors.lastname: Han
authors.affiliation: Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Department of Urology, Shanghai General Hospital Affiliated to Nanjing Medical University, Shanghai 200080, China; Institute of Urology, Shanghai Jiao Tong University, Shanghai 200080, China. Electronic address: xsjurologist@163.com.
authors.forename: Shu-Jie
authors.initials: SJ
authors.lastname: Xia
authors.affiliation: Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Institute of Urology, Shanghai Jiao Tong University, Shanghai 200080, China. Electronic address: drzhaofujun@yahoo.com.
authors.forename: Fu-Jun
authors.initials: FJ
authors.lastname: Zhao
mesh_terms: D020413:3' Untranslated Regions; D059002:Androgen Receptor Antagonists / Q000378:metabolism; D001665:Binding Sites; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D014176:Protein Biosynthesis; D000072417:Protein Domains; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D000092468:Bromodomain Containing Proteins
chemical_list: D020413:3' Untranslated Regions; D059002:Androgen Receptor Antagonists; D035683:MicroRNAs; D020033:Protein Isoforms; D012333:RNA, Messenger; D011944:Receptors, Androgen; D011988:Receptors, Thyroid Hormone; D014157:Transcription Factors; C099139:BRD8 protein, human; D000092468:Bromodomain Containing Proteins; C552431:MIRN185 microRNA, human
keywords: Androgen receptor (AR); Bromodomain containing 8 (BRD8); Prostate cancer; miR-185