title: Emerging role of microRNA-27a in human malignant glioma cell survival via targeting of prohibitin.
abstract: MicroRNAs (miRs) function as oncogenes and tumor suppressors, and have roles in most cellular processes. To date, the possible role of miR-27a, which is part of the miR-23a/27a/24-2 cluster, in malignant gliomas has remained elusive. Therefore, the present study aimed to explore the role of miR-27a in glioma and its potential target. Through transfection with miR-27a inhibitor or oligonucleotide mimics, the impact of miR-27a silencing or overexpression on the growth, apoptosis, cell cycle and invasiveness of U251 and U87MG cells was examined in vitro. The present study initially identified the potential target of miR-27a in glioma cells through a bioinformatics analysis, which was used for screening of the literature on the proteomics of gliomas. Prohibitin (PHB) was then confirmed as a target by absolute luciferase reporter assays, quantitative real-time polymerase chain reaction and western blot analysis. Treatment with miR-27a mimics oligonucleotides suppressed U251 cell proliferation, promoted apoptosis by inducing G2/M phase arrest, and impaired the invasive potential of U251 cells in vitro. In addition, miR-27a expression was downregulated in glioma tissues. A PHB-3'-untranslated region luciferase reporter assay confirmed PHB as a direct target gene of miR-27a. PHB mRNA expression was reversely correlated with levels of miR-27a in U251 cells. Overexpression of miR-27a in U251 cells at 72 h and 96 h post‑transfection with miR-27a mimics significantly decreased PHB protein expression by 17.2% and 43.9%, respectively. In conclusion, miR-27a was shown to be a significant tumor suppressor by targeting and decreasing PHB protein expression in glioma U251 cells. miR-27a targeting of PHB may be a novel potential therapeutic strategy for glioma.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Institute of Transfusion Research, Shaanxi Blood Center, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Bao
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Tuo
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Chang-Wang
authors.initials: CW
authors.lastname: Du
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Mao-De
authors.initials: MD
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D000091402:Prohibitins; D012097:Repressor Proteins / Q000096:biosynthesis*
chemical_list: C531388:MIRN27 microRNA, human; D035683:MicroRNAs; C000717328:PHB protein, human; D000091402:Prohibitins; D012097:Repressor Proteins