title: MiR-218 sensitizes glioma cells to apoptosis and inhibits tumorigenicity by regulating ECOP-mediated suppression of NF-κB activity.
abstract: BACKGROUND
  Malignant gliomas are the most common and deadly primary brain tumors in adults. Increasing evidence has indicated that microRNAs (miRNAs) have an influence on the regulation of apoptotic cell signaling. Downregulation of miRNA 218 (miR-218) has been indicated in human glioma specimens. Here, we investigate the function of miR-218 in apoptosis and tumor growth of glioma cells.
  
  
  METHODS
  The expression of miR-218 was detected by real-time quantitative reverse transcriptase PCR. The effects of miR-218 on glioma cell proliferation and tumorigenicity were investigated by in vitro clonogenicity and in vivo xenograft assay. Apoptosis was evaluated by flow cytometric analysis and assay by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling. The downstream targets of miR-218 were identified by bioinformatics analysis and further validated by Western blot and luciferase reporter assay.
  
  
  RESULTS
  Overexpression of miR-218 induces glioma cell apoptosis and inhibits glioma cell viability, proliferation, and tumorigenicity. Epidermal growth factor receptor-coamplified and overexpressed protein (ECOP) was identified as a functional downstream target of miR-218, which can regulate transcriptional activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and associated with apoptotic response. Ectopic expression of ECOP rescued the glioma cells from miR-218-induced apoptosis and increased NF-κB activity.
  
  
  CONCLUSIONS
  These results suggest that miR-218 sensitizes glioma cells to apoptosis by regulating ECOP-mediated suppression of NF-κB activity, which may provide novel opportunities for glioma therapy.
authors.affiliation: Department of Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, Anhui 241001, China.
authors.forename: Hongping
authors.initials: H
authors.lastname: Xia
authors.forename: Yukui
authors.initials: Y
authors.lastname: Yan
authors.forename: Minghua
authors.initials: M
authors.lastname: Hu
authors.forename: Yaxian
authors.initials: Y
authors.lastname: Wang
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Dai
authors.forename: Jianming
authors.initials: J
authors.lastname: Chen
authors.forename: Guangfu
authors.initials: G
authors.lastname: Di
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Chen
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control; D049109:Cell Proliferation; D005434:Flow Cytometry; D005910:Glioma / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: C547471:MIRN218 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors; C500380:VOPP1 protein, human