title: miR-370 modulates insulin receptor substrate-1 expression and inhibits the tumor phenotypes of oral carcinoma.
abstract: BACKGROUND
  MicroRNAs play important roles in carcinogenesis. A preliminary screening study suggested that down-regulation of miR-370 occurs in oral squamous cell carcinoma (OSCC) tissue. Insulin receptor substratre-1 (IRS-1) is the substrate of insulin-like growth factor receptor (IGFR), which modulates AKT/mTOR activation in malignancies. The relationship between miR-370 and IRS-1, and their functional roles in OSCC pathogenesis are unclear.
  
  
  METHODS
  Primary OSCC specimens were examined for miR-370 expression. Exogenous expression of miR-370 was established using both stable subclones and transient expression, and these were used to gain insights into miR-370's functions in OSCC cells. Knockdown of miR-370 and IRS-1 was also carried out in OSCC cells using a small interference oligonucleotide approach.
  
  
  RESULTS
  Squamous cell carcinoma tissues with perineural invasion had lowered miR-370 expression compared with contrasting OSCC. OSCC cells also exhibited lower miR-370 expression than normal oral keratinocytes, and this can be reversed by treatment with 5-aza-2'-deoxycytidine. Exogenous miR-370 expression decreases the migration and anchorage-independent growth of OSCC cells, which implies a suppressor role for miR-370. The enhancement of anchorage-independent growth of OSCC cells through miR-370 inhibiting can be reduced by knockdown of IRS-1 expression.
  
  
  CONCLUSIONS
  This study concludes that miR-370 is able to target IRS-1 for oral tumorigenesis.
authors.affiliation: Department of Dentistry, National Yang-Ming University, Taipei, Taiwan.
authors.forename: K-W
authors.initials: KW
authors.lastname: Chang
authors.forename: T-H
authors.initials: TH
authors.lastname: Chu
authors.forename: N-R
authors.initials: NR
authors.lastname: Gong
authors.forename: W-F
authors.initials: WF
authors.lastname: Chiang
authors.forename: C-C
authors.initials: CC
authors.lastname: Yang
authors.forename: C-J
authors.initials: CJ
authors.lastname: Liu
authors.forename: C-H
authors.initials: CH
authors.lastname: Wu
authors.forename: S-C
authors.initials: SC
authors.lastname: Lin
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D063646:Carcinogenesis / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002448:Cell Adhesion / Q000235:genetics; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000502:physiology*; D015603:Keratinocytes / Q000187:drug effects / Q000473:pathology; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D009062:Mouth Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D051058:Oncogene Protein v-akt / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000502:physiology
chemical_list: C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; C526503:MIRN370 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D000077209:Decitabine; D015254:DNA Modification Methylases; C546842:MTOR protein, human; D051058:Oncogene Protein v-akt; D058570:TOR Serine-Threonine Kinases; D001374:Azacitidine