title: Growth of glioblastoma is inhibited by miR-133-mediated EGFR suppression.
abstract: Glioblastoma multiforme (GBM) is a severe and highly lethal brain cancer, which malignancy largely stems from its growing in a relatively restrained area in the brain. Hence, the understanding of the molecular regulation of the growth of GBM is critical for improving its treatment. Dysregulation of microRNAs (miRNAs) has recently been shown to contribute to the development of GBM, whereas the role of miR-133 in GBM is unknown. Here, by qualitative reverse transcription polymerase chain reaction (RT-qPCR), we detected lower miR-133 levels in GBM tissues, compared to the paired normal brain tissue. We overexpressed or inhibited miR-133 in GBM cells. Cell growth and apoptosis were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. We found that overexpression of miR-133 decreased GBM cell growth and increased cell apoptosis, while depletion of miR-133 increased cell growth and decreased cell apoptosis. Bioinformatic analysis was performed, showing that miR-133 may target the 3'-untranslated region (3'-UTR) of the epidermal growth factor receptor (EGFR) that transduces cell growth signals. Further, the protein translation inhibition of EGFR by miR-133 was confirmed by a dual luciferase reporter assay. Together, these data suggest that reduced miR-133 levels in GBM tissues promotes cell growth and decreases cell apoptosis, possibly through targeting mRNA of EGFR to suppress its translation.
authors.affiliation: Department of Neurosurgery, Minhang Hospital, Fudan University, 170 Xinsong Road, Shanghai, 201199, China.
authors.forename: Fulin
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, 999 Xiwang Road, Shanghai, 201800, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, 999 Xiwang Road, Shanghai, 201800, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, 999 Xiwang Road, Shanghai, 201800, China. pifeng_jia@163.com.
authors.forename: Pifeng
authors.initials: P
authors.lastname: Jia
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger
chemical_list: C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Epidermal growth factor receptor (EGFR); Glioblastoma multiforme (GBM); Growth; miR-133; microRNAs (miRNA)