title: Tumor suppressor miR-181c attenuates proliferation, invasion, and self-renewal abilities in glioblastoma.
abstract: Glioblastoma multiforme (GBM) is well known for its aggressiveness, but the underlying mechanisms are unclear, limiting the treatment. In the present study, we showed that miR-181c, a commonly downregulated miRNA in GBM reported by several miRNA profiles, was associated with the mesenchymal subtype of GBM and predicted the outcome for patients from a GBM cohort (n=518) obtained from The Cancer Genome Atlas database. A multivariate analysis showed that miR-181c was an independent prognostic indicator for GBM patients. Quantitative reverse transcription PCR showed that miR-181c was expressed poorly in neurospheres of glioma cells that resemble glioma stem cells. Proliferation and invasion assays showed that miR-181c also blocked the proliferation and invasion abilities of glioma cells. Limiting dilution and colony formation assays showed that miR-181c attenuated the self-renewal ability of glioma cells. Finally, investigation of the mechanism defined Notch2, a key molecular of Notch signaling, as the functional downstream target of miR-181c. An inverse correlation was found between miR-181c and Notch2 in glioma cells and verified in fresh glioma samples. Taken together, the present study showed that miR-181c can be considered a valuable indicator for the outcome of GBM patients. miR-181c acts as a tumor suppressor that attenuates proliferation, invasion, and self-renewal capacities by downregulation of Notch2 in glioma cells.
authors.affiliation: aDepartment of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University bDepartment of Neurosurgery, Chongqing Cancer Institute, Chongqing, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ruan
authors.forename: Silong
authors.initials: S
authors.lastname: Lou
authors.forename: Qinbi
authors.initials: Q
authors.lastname: Dai
authors.forename: Deqiang
authors.initials: D
authors.lastname: Mao
authors.forename: Jia
authors.initials: J
authors.lastname: Ji
authors.forename: Xiaochuan
authors.initials: X
authors.lastname: Sun
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D051883:Receptor, Notch2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D051883:Receptor, Notch2