title: The Down-Regulation of MicroRNA-497 Contributes to Cell Growth and Cisplatin Resistance Through PI3K/Akt Pathway in Osteosarcoma.
abstract: BACKGROUND
  Down-expression of microRNA-497 (miR-497) was often found in malignancies. The purposes of this study were to determine the expression of miR-497 in human osteosarcoma and to establish the association between miR-497 expression with cell survival and the sensitivity to cisplatin in human osteosarcoma cells.
  
  
  METHODS
  The effects of ectopic miR-497 expression on the cell survival and cisplatin sensitivity in osteosarcoma cells were measured by the Cell Counting Kit-8 (CCK-8) assay. Quantitative real-time PCR (qRT-PCR) was utilized to determine the expression of miR-497. The effects of ectopic miR-497 expression on the expression of VEGFA, Akt and p-Akt were determined by western blot.
  
  
  RESULTS
  Real-time quantitative PCR analysis revealed that miR-497 was significantly down-regulated in osteosarcoma tissues and in the osteosarcoma cell line SAOS-2 compared with adjacent nontumorous osteosarcoma tissues and normal human osteoblasts. Up-regulation of miR-497 inhibited cell survival and enhanced the sensitivity to cisplatin in osteosarcoma cells. In addition, knockdown of miR-497 induced osteosarcoma cells growth and cisplatin resistance. Luciferase reporter assay and western blot confirmed that VEGFA was a direct target of miR-497. PI3K inhibitor LY294002 abrogated miR-497 inhibitors induced cisplatin resistance.
  
  
  CONCLUSIONS
  Taken together, our results suggest that miR-497 modulates the sensitivity to cisplatin at least in part through PI3K/Akt pathway in osteosarcoma cells.
authors.affiliation: Department of Clinical Laboratory Diagnosis, Soochow University Affiliated Children's Hospital of Soochow University, Suzhou, China.
authors.forename: Xue-jun
authors.initials: XJ
authors.lastname: Shao
authors.forename: Mei-hua
authors.initials: MH
authors.lastname: Miao
authors.forename: Jun
authors.initials: J
authors.lastname: Xue
authors.forename: Jian
authors.initials: J
authors.lastname: Xue
authors.forename: Xue-qiang
authors.initials: XQ
authors.lastname: Ji
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D001859:Bone Neoplasms / Q000201:enzymology / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects / Q000235:genetics*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000633:toxicity*; D015536:Down-Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D012516:Osteosarcoma / Q000201:enzymology / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C559640:MIRN497 microRNA, human; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D002945:Cisplatin