title: MiR-125b acts as an oncogene in glioblastoma cells and inhibits cell apoptosis through p53 and p38MAPK-independent pathways.
abstract: BACKGROUND
  We have recently identified miR-125b upregulation in glioblastoma (GMB). The aim of this study is to determine the correlation between miR-125b expression and malignant grades of glioma and the genes targeted by miR-125b.
  
  
  METHODS
  Real-time PCR was employed to measure the expression level of miR-125b. Cell viability was evaluated by cell growth and colony formation in soft-agar assays. Cell apoptosis was determined by Hoechst 33342 staining and AnnexinV-FITC assay. The Luciferase assay was used to confirm the actual binding sites of p38MAPK mRNA. Western blot was used to detect the gene expression level.
  
  
  RESULTS
  The expression level of miR-125b is positively correlated with the malignant grade of glioma. Ectopic expression of miR-125b promotes the proliferation of GMB cells. Knockdown of endogenous miR-125b inhibits cell proliferation and promotes cell apoptosis. Further studies reveal that p53 is regulated by miR-125b. However, downregulation of the endogenous miR-125b also results in p53-independent apoptotic pathway leading to apoptosis in p53 mutated U251 cells and p53 knockdown U87 cells. Moreover, p38MAPK is also regulated by miR-125b and downregulation of miR-125b activates the p38MAPK-induced mitochondria apoptotic pathway.
  
  
  CONCLUSIONS
  High-level expression of miR-125b is associated with poor outcomes of GMB. MiR-125b may have an oncogenic role in GMB cells by promoting cell proliferation and inhibiting apoptosis.
authors.affiliation: Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China.
authors.forename: N
authors.initials: N
authors.lastname: Wu
authors.forename: X
authors.initials: X
authors.lastname: Lin
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.forename: L
authors.initials: L
authors.lastname: Zheng
authors.forename: L
authors.initials: L
authors.lastname: Xiao
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Ge
authors.forename: S
authors.initials: S
authors.lastname: Cao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002478:Cells, Cultured; D002648:Child; D005260:Female; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D009857:Oncogenes / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
chemical_list: C531888:MIRN125 microRNA, human; D035683:MicroRNAs; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D048051:p38 Mitogen-Activated Protein Kinases