MicroRNAs and glioblastoma: roles in core signalling pathways and potential clinical implications.
Bottom Line: MicroRNAs (miRNAs) are endogenously expressed small non-coding RNAs that act as post-transcriptional regulators of gene expression.Dysregulation of these molecules has been indicated in the development of many cancers.It was repeatedly found that miRNAs are involved in important signalling pathways, which play roles in crucial cellular processes, such as proliferation, apoptosis, cell cycle regulation, invasion, angiogenesis and stem cell behaviour.
Affiliation: Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Brno, Czech Republic.Show MeSH
Related in: MedlinePlus
Mentions: Li et al. studied the role of miR-34a in human brain tumours with a special focus on glioblastomas. They found that miR-34a inhibits Notch-1 and Notch-2 protein expression and 3′-UTR reporter activities as well as CDK6 and c-Met protein expression in glioma cells. They observed for the first time that average pre-miR-34a expression is down-regulated in human glioblastoma tissues when compared to normal human brain . Other studies showed that miR-34a expression was higher in wild-type p53 glioblastoma tissues compared to mutant p53 glioblastoma; miR-34a acts as a tumour suppressor in p53-mutant glioma cells U251, partially through regulating SIRT1 . Transfection of miR-34a into tested glioblastoma cell lines strongly inhibited cell proliferation, cell cycle, cell survival, cell invasion and in vivo glioblastoma xenograft growth; however, the treatment did not affect human astrocyte cell survival and cell cycle. Forced c-Met and Notch-1/2 expression partially rescued the effects of miR-34a on the cell cycle and cell death in gliomas, respectively  (summarized in Fig. 3).
Affiliation: Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Brno, Czech Republic.