title: MiR-203 down-regulates Rap1A and suppresses cell proliferation, adhesion and invasion in prostate cancer.
abstract: OBJECTIVE
  Evidence supports an important role for miR-203 in the regulation of the proliferation, migration and invasion of prostate cancer (PCa) cells. However, the exact mechanisms of miR-203 in PCa are not entirely clear.
  
  
  METHODS
  We examined the expression of miR-203 in prostate cancer tissues, adjacent normal tissues, PCa cell lines and normal prostate epithelial cells by qRT-PCR. Then, the effects of miR-203 or Rap1A on proliferation, adhesion and invasion of PCa cells were assayed using CKK-8, adhesion analysis, and transwell invasion assays. Luciferase reporter assay was performed to assess miR-203 binding to Rap1A mRNA. Tumor growth was assessed by subcutaneous inoculation of cells into BALB/c nude mice.
  
  
  RESULTS
  Here, we confirmed that the expression of miR-203 was significantly downregulated in prostate cancer specimens compared with matched adjacent normal prostate specimens. Mechanistic dissection revealed that miR-203 mediated cell proliferation, adhesion and invasion in vitro, and tumor growth in vivo, as evidenced by reduced RAC1, p-PAK1, and p-MEK1 expression. In addition, we identified Rap1A as a direct target suppressed by miR-203, and there was an inverse relationship between the expression of miR-203 and Rap1A in PCa. Knockdown of Rap1A phenocopied the effects of miR-203 on PCa cell growth and invasion. Furthermore, Rap1A over-expression in PCa cells partially reversed the effects of miR-203-expression on cell adhesion and invasion.
  
  
  CONCLUSIONS
  These findings provide further evidence that a crucial role for miR-203 in inhibiting metastasis of PCa through the suppression of Rap1A expression.
authors: Department of Urology, Tongji Hospital, Tongji University School of Medicine, NO 389 Xinchun road, Shanghai, 200065, China. zhuxufifa2007@163.com.
authors: Jun
authors: J
authors: Xiang
authors: Department of Urology, Tongji Hospital, Tongji University School of Medicine, NO 389 Xinchun road, Shanghai, 200065, China. 071101023@fudan.edu.cn.
authors: Cuidong
authors: C
authors: Bian
authors: The Experimental Center of Basic Medical, Shanghai Medical College, Fudan University, Shanghai, 200032, China. wh91351@126.com.
authors: Hao
authors: H
authors: Wang
authors: Department of Urology, Tongji Hospital, Tongji University School of Medicine, NO 389 Xinchun road, Shanghai, 200065, China. YanWangArmy@163.com.
authors: Shengsong
authors: S
authors: Huang
authors: Department of Urology, Tongji Hospital, Tongji University School of Medicine, NO 389 Xinchun road, Shanghai, 200065, China. wudeng123long@163.com.
authors: Denglong
authors: D
authors: Wu
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015536:Down-Regulation; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D020827:rap1 GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: C546703:MIRN203 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D020827:rap1 GTP-Binding Proteins
references: Cancer Prev Res (Phila). 2011 Jan;4(1):76-86
references: 21071579
references: J Biol Chem. 2005 Feb 11;280(6):5022-31
references: 15569673
references: Nat Rev Genet. 2010 Sep;11(9):597-610
references: 20661255
references: J Exp Clin Cancer Res. 2014;33:72
references: 25200485
references: Nature. 2008 Mar 13;452(7184):225-9
references: 18311128
references: J Exp Clin Cancer Res. 2012;31:38
references: 22546315
references: PLoS One. 2012;7(6):e39167
references: 22723956
references: J Biol Chem. 1988 Dec 15;263(35):18965-71
references: 3143720
references: Curr Opin Cell Biol. 2005 Apr;17(2):123-8
references: 15780587
references: Prostate. 2012 Sep 15;72(13):1469-77
references: 22298119
references: Cell. 2005 Jan 14;120(1):15-20
references: 15652477
references: Cancer Res. 2009 Jun 15;69(12):4962-8
references: 19470770
references: Oncogene. 2009 Sep 17;28(37):3307-19
references: 19597465
references: Nat Immunol. 2003 Aug;4(8):741-8
references: 12845325
references: Oncogene. 2000 Dec 7;19(52):6074-81
references: 11146560
references: Genes Cancer. 2013 Jul;4(7-8):285-96
references: 24167656
references: Genes Cancer. 2011 Jul;2(7):720-7
references: 22207897
references: J Cancer. 2013;4(1):66-83
references: 23386906
references: Cancer Res. 2011 Feb 15;71(4):1313-24
references: 21212412
references: PLoS One. 2013;8(4):e61858
references: 23613955
references: J Clin Oncol. 2007 Apr 20;25(12):1596-605
references: 17404365
references: Cancer Res. 2011 Mar 1;71(5):1956-67
references: 21343391
references: Rev Urol. 2007;9 Suppl 2:S13-8
references: 17554405
references: Cell. 2009 Feb 20;136(4):656-68
references: 19239887
references: Int J Cell Biol. 2012;2012:676731
references: 22505933
references: Cancer Cell. 2008 Jun;13(6):496-506
references: 18538733
references: Epigenetics. 2014 Jan;9(1):129-41
references: 24149370
references: Cancer Res. 1999 Sep 1;59(17):4180-4
references: 10485450
references: Cancer Res. 2009 Apr 1;69(7):2941-9
references: 19318561
references: Ann Surg Oncol. 2012 Jul;19 Suppl 3:S656-64
references: 22311119
references: Cell Cycle. 2011 Apr 1;10(7):1121-31
references: 21368580
references: PLoS One. 2013;8(9):e73268
references: 24039897
references: Carcinogenesis. 2012 Nov;33(11):2018-25
references: 22902544
references: J Exp Clin Cancer Res. 2013;32:9
references: 23406686
references: Oncogene. 2013 Jan 17;32(3):277-85
references: 22391564
references: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references: 21296855
references: Clin Cancer Res. 2011 Aug 15;17(16):5287-98
references: 21159887
references: PLoS One. 2013;8(9):e73985
references: 24040137
references: Acta Biochim Biophys Sin (Shanghai). 2010 Jun 15;42(6):363-9
references: 20539944