title: MiR200c targets IRS1 and suppresses prostate cancer cell growth.
abstract: BACKGROUND
  The downregulation of the tumor suppressor miR200c plays important roles in many malignant tumors. This study aims to show that miR200c is a posttranscriptional regulator of insulin receptor substrate 1 (IRS1) and over-expression of miR200c suppresses prostate cancer cell growth.
  
  
  METHODS
  Bioinformatics analysis was used to show potential post-translational regulation of IRS1 by miR200c. Dual reporter gene assays were chosen to test the binding of miR200c to the potential seed sequences in IRS1 3'UTR. RT-PCR, Q-PCR and western blot were applied to determine the regulation effect of miR200c on IRS1. CCK8 assay, soft agar assay, trypan blue exclusion assay and flow cytometric analysis were used to measure the biological effects of miR200c on prostate cancer cell proliferation and apoptosis.
  
  
  RESULTS
  The 449-455 nt, 3061-3067 nt, and 3096-3102 nt of the IRS1 3'-UTR were identified as three potential seed sequences for miR200c. MiR200c directly binds to IRS1 through the seed sequences in IRS1 3'-UTR. Artificial overexpression of miR200c significantly downregulated the mRNA and protein levels of IRS1, together with decreased cell proliferation and increased cell death of PC3 and DU145 cells.
  
  
  CONCLUSIONS
  Our results suggest that miR200c plays crucial roles in prostate cancer by post-transcriptional regulation of IRS1. The mir200c/IRS1 pathway may be a potential therapeutic target to prevent prostate cancer cell growth.
authors: Department of Pathology and Laboratory of Pathology, State Key Laboratory of Biotherapy; West China Hospital, West China Medical School, Sichuan University, Chengdu, P.R. China; Department of Pathology, Shandong Provincial Hospital, Shandong University, Jinan, P.R. China.
authors: Wenjing
authors: W
authors: Su
authors: Miao
authors: M
authors: Xu
authors: Xueqin
authors: X
authors: Chen
authors: Ling
authors: L
authors: Nie
authors: Ni
authors: N
authors: Chen
authors: Jing
authors: J
authors: Gong
authors: Mengni
authors: M
authors: Zhang
authors: Zhengzheng
authors: Z
authors: Su
authors: Lei
authors: L
authors: Huang
authors: Qiao
authors: Q
authors: Zhou
mesh_terms: D017209:Apoptosis / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D049108:Cell Enlargement; D045744:Cell Line, Tumor; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000096:biosynthesis*; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger