title: Downregulation of miR-452 promotes stem-like traits and tumorigenicity of gliomas.
abstract: OBJECTIVE
  miR-452 is reported to be required for neural crest stem cell differentiation during neural crest development. However, the biologic role of miR-452 in gliomas remains unclear. The aim of the present study was to evaluate the effect of miR-452 on the stem-like properties and tumorigenesis of glioma cells.
  
  
  METHODS
  The expression of miR-452 was examined in glioma cells and glioma tissues using real-time PCR. The effects of miR-452 on stem-like traits and tumorigenesis were investigated in vitro and in vivo using patient-derived glioma cells and glioma cell lines. Western blotting and luciferase reporter assays were conducted to examine the negative regulation of Bmi-1, LEF1, and TCF4 by miR-452. The methylation of the miR-452 promoter region was examined by bisulfite genomic sequencing PCR.
  
  
  RESULTS
  miR-452 was markedly downregulated in glioma cells and clinical glioma tissues. miR-452 levels were inversely correlated with World Health Organization (WHO) grades and patient survival. miR-452 directly targeted and suppressed multiple stemness regulators, including Bmi-1, LEF1, and TCF4, resulting in reduced stem-like traits and tumorigenesis of glioma cells in vitro and in vivo. Furthermore, we showed that downregulation of miR-452 in gliomas was caused by hypermethylation of its promoter region.
  
  
  CONCLUSIONS
  Downregulation of miR-452 plays an important role in promoting the stem-like traits and tumorigenesis of gliomas and may represent a novel prognostic biomarker and therapeutic target for the disease.
authors.affiliation: State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Cancer Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Liu
authors.forename: Kun
authors.initials: K
authors.lastname: Chen
authors.forename: Jueheng
authors.initials: J
authors.lastname: Wu
authors.forename: Ling
authors.initials: L
authors.lastname: Shi
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.forename: Shiyuan
authors.initials: S
authors.lastname: Cheng
authors.forename: Mengfeng
authors.initials: M
authors.lastname: Li
authors.forename: Libing
authors.initials: L
authors.lastname: Song
mesh_terms: D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D019175:DNA Methylation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D019655:Quantitative Trait, Heritable
chemical_list: C574051:MIRN452 microRNA, human; D035683:MicroRNAs