title: Down-regulation of miR-126 is associated with colorectal cancer cells proliferation, migration and invasion by targeting IRS-1 via the AKT and ERK1/2 signaling pathways.
abstract: BACKGROUND
  Colorectal carcinoma (CRC) is one of the leading causes of cancer-related mortality worldwide. MicroRNAs (miRNAs, miRs) play important roles in carcinogenesis. MiR-126 has been shown to be down-regulated in CRC. In this study, we identified the potential effects of miR-126 on some important biological properties of CRC cells and clarified the regulation of insulin receptor substrate 1 (IRS-1) and its possible signaling pathway by miR-126.
  
  
  METHODS
  The effect of miR-126 on IRS-1, AKT, and ERK1/2 expression was assessed in the CRC cell lines HT-29 and HCT-116 with a miR-126 mimic or inhibitor to increase or decrease miR-126 expression. Furthermore, the roles of miR-126 in regulation of the biological properties of CRC cells were analyzed with miR-126 mimic or inhibitor-transfected cells. The 3'-untranslated region (3'-UTR) of IRS-1 regulated by miR-126 was analyzed by using a dual-luciferase reporter assay.
  
  
  RESULTS
  We found that IRS-1 is the functional downstream target of miR-126 by directly targeting the 3'-UTR of IRS-1. Endogenous miR-126 and exogenous miR-126 mimic inhibited IRS-1 expression. Furthermore, gain-of-function or loss-of-function studies showed that over-expression of miR-126 down-regulated IRS-1, suppressed AKT and ERK1/2 activation, CRC cells proliferation, migration, invasion, and caused cell cycle arrest, but had no effect on cell apoptosis. Knockdown of miR-126 promoted these processes in HCT-116 cells and promoted AKT and ERK1/2 activation by up-regulating the expression of the IRS-1 protein.
  
  
  CONCLUSIONS
  MiR-126 may play roles in regulation of the biological behavior of CRC cells, at least in part, by targeting IRS-1 via AKT and ERK1/2 signaling pathways.
authors: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China ; Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong Province, China.
authors: Yu
authors: Y
authors: Zhou
authors: Xiao
authors: X
authors: Feng
authors: Ya-ling
authors: YL
authors: Liu
authors: Shi-cai
authors: SC
authors: Ye
authors: Hao
authors: H
authors: Wang
authors: Wen-kai
authors: WK
authors: Tan
authors: Ting
authors: T
authors: Tian
authors: Yu-mei
authors: YM
authors: Qiu
authors: He-sheng
authors: HS
authors: Luo
mesh_terms: D063646:Carcinogenesis; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000473:pathology*; D015536:Down-Regulation; D004789:Enzyme Activation; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle / Q000235:genetics
chemical_list: D055504:Insulin Receptor Substrate Proteins; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3