Tumor Suppressor MiRNA-181c Attenuates Proliferation, Invasion And Self-Renewal Abilities In Glioblastoma

Glioblastoma multiforme (GBM) is an aggressive and lethal malignant tumor of the central nervous system worldwide, which is renowned for its fast growing and strong invasion abilities with the underlying mechanisms unveiled, limiting the treatment.In our present study, we showed that miRNA-181c, a commonly down-regulated miRNA in GBM reported by several miRNA profiles, was associated with mesenchymal subtype of GBM and predicted the outcome for patients from GBM cohort (n=518) obtained from The Cancer Genome Atlas (TCGA) database. A multivariate analysis revealed that miRNA-181c was an independent prognostic indicator for GBM patients. Quantitative reverse transcription PCR showed that miRNA-181c was lowly expressed in neurospheres of glioma cells. Proliferation and invasion assays demonstrated that miRNA-181c also blocked the proliferation and invasion abilities of glioma cells. Limiting dilution and colony formation assays revealed that miRNA-181c attenuated the self-renewal ability of glioma cells. Finally, mechanism investigation defined Notch2, a key molecular of Notch signaling, as the functional downstream target of miRNA-181c. Inversed correlation between miRNA-181c and Notch2 was proved in glioma cells. Taken together, our present study showed that miRNA-181c was considered as a valuable indicator for the outcome of GBM patients and served as a tumor suppressor that attenuated proliferation, invasion and self-renewal capacities by down-regulation of Notch2 in glioma cells.