title: Upregulation of miR-181a suppresses the formation of glioblastoma stem cells by targeting the Notch2 oncogene and correlates with good prognosis in patients with glioblastoma multiforme.
abstract: Glioblastoma stem-like cells (GSCs) are responsible for the initiation and progression of glioblastoma multiforme (GBM), and microRNAs (miRNAs) play an important role in this disease. However, the mechanisms underlying the role of miRNAs in the stemness of GSCs have not been completely elucidated. We previously showed that miR-181a is downregulated in GBM and may predict prognosis in patients with this disease. Here, we demonstrate that the upregulation of miR-181a suppressed GSC formation and inhibited GBM tumorigenesis by targeting the Notch2 oncogene. We found that miR-181a was downregulated in GSCs derived from human glioblastoma U87MG and U373MG cells. The high expression of miR-181a inhibited the levels of stemness-related markers CD133 and BMI1, attenuated sphere proliferation, promoted cell apoptosis, and reduced the tumorigenicity of GSCs. MiR-181a decreased the expression of Notch2 by targeting the 3'-untranslated region of its mRNA. Notch2 overexpression inhibited the effects of miR-181a downregulation on GSCs, and was negatively correlated with miR-181a expression. Moreover, high Notch2 expression together with low miR-181a expression was correlated with a shorter median overall survival for GBM patients. Together, these data show that miR-181a may play an essential role in GSC formation and GBM progression by targeting Notch2, suggesting that Notch2 and miR-181a have potential prognostic value as tumor biomarkers in GBM patients.
authors.affiliation: Department of Neurology, Hainan General Hospital, Haikou 570311, China.
authors.forename: Shi-Xiong
authors.initials: SX
authors.lastname: Huang
authors.affiliation: Department of Neurology, Hainan General Hospital, Haikou 570311, China.
authors.forename: Zhong-Yan
authors.initials: ZY
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Hainan General Hospital, Haikou 570311, China.
authors.forename: Guo-Hu
authors.initials: GH
authors.lastname: Weng
authors.affiliation: Department of Neurology, Hainan General Hospital, Haikou 570311, China.
authors.forename: Xiang-Ying
authors.initials: XY
authors.lastname: He
authors.affiliation: Department of Neurology, Hainan General Hospital, Haikou 570311, China.
authors.forename: Chan-Ji
authors.initials: CJ
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Hainan General Hospital, Haikou 570311, China.
authors.forename: Chuan-Yi
authors.initials: CY
authors.lastname: Fu
authors.affiliation: Department of Neurology, Hainan General Hospital, Haikou 570311, China.
authors.forename: Zhi-Yan
authors.initials: ZY
authors.lastname: Sui
authors.affiliation: Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, College of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
authors.forename: Yu-Shui
authors.initials: YS
authors.lastname: Ma
authors.affiliation: Department of Neurology, Hainan General Hospital, Haikou 570311, China. Electronic address: ltao829@126.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality*; D045744:Cell Line, Tumor; D002681:China / Q000453:epidemiology; D005909:Glioblastoma / Q000378:metabolism* / Q000401:mortality*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D051883:Receptor, Notch2 / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013223:Statistics as Topic; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; C497764:NOTCH2 protein, human; D051883:Receptor, Notch2
keywords: Biomarker; GBM; GSC; Notch2; miR-181a