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
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Mentions: Papagiannakopoulos et al. reported that p53, TGF-β and mitochondrial apoptotic networks are de-repressed in response to miR-21 knockdown. They published a panel of genes involved in particular pathways and simultaneously modulated by miR-21 treatment. From this panel, p63, JMY, TP53BP2, HNRPK, TOPORS, IGFB3, APAF1, PPIF, TGFBR2/3, DAXX, HNRNPK were predicted to be direct targets of miR-21 that can stabilize p53 protein levels by interfering with MDM2 and/or act as p53 transcriptional cofactors . Inhibition of miR-21 increased also endogenous levels of PDCD4 in human glioma cell lines and activated caspases 9 and 3, which may be mediated by modulating multiple potential target genes, such as TIMP3 [22, 23]. Protein PDCD4 inhibits translation by its interaction with the factor that initiates translation of eIF4A and eIF4G. PDCD4 also inhibits proliferation via activation of p21CIP1. In addition, specific inhibition of miR-21 led to elevated levels of RECK and TIMP3 and therefore reduced MMP activities in vitro and in model of gliomas in nude mice. Consequently, down-regulation of miR-21 decreased migratory and invasive abilities in glioma cells (Fig. 2) .
Affiliation: Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Brno, Czech Republic.