MicroRNA in Glioblastoma: An Overview

Abstract

Glioblastoma is the most aggressive brain tumor and, even with the current multimodal therapy, is an invariably lethal cancer with a life expectancy that depends on the tumor subtype but, even in the most favorable cases, rarely exceeds 2 years. Epigenetic factors play an important role in gliomagenesis, are strong predictors of outcome, and are important determinants for the resistance to radio- and chemotherapy. The latest addition to the epigenetic machinery is the noncoding RNA (ncRNA), that is, RNA molecules that are not translated into a protein and that exert their function by base pairing with other nucleic acids in a reversible and nonmutational mode. MicroRNAs (miRNA) are a class of ncRNA of about 22 bp that regulate gene expression by binding to complementary sequences in the mRNA and silence its translation into proteins. MicroRNAs reversibly regulate transcription through nonmutational mechanisms; accordingly, they can be considered as epigenetic effectors. In this review, we will discuss the role of miRNA in glioma focusing on their role in drug resistance and on their potential applications in the therapy of this tumor.

HMGB3 promotes the proliferation and metastasis of glioblastoma and is negatively regulated by miR‐200b‐3p and miR‐200c‐3p

“…Recent studies have highlighted the pivotal roles of miRNAs in regulating GBM development and their potential as targets for cancer therapy . In order to reveal the regulatory mechanism of HMGB3 in GBM, we first sought to determine whether any relevant miRNAs regulate HMGB3.…”

“…Recent studies have highlighted the pivotal roles of miRNAs in regulating GBM development and their potential as targets for cancer therapy. 26 In order to reveal the regulatory mechanism of HMGB3 in GBM, we first sought to determine whether any relevant miRNAs regulate HMGB3. Using the miRNA target prediction algorithm TargetScan (www.targetscan.org), we determined that HMGB3 was a predicted target of miR-200b-3p and miR-200c-3p ( Figure 5A).…”

Long noncoding RNA gastric cancer‐associated transcript 3 plays oncogenic roles in glioma through sponging miR‐3127‐5p

“…miRNAs are small non-protein-encoding RNAs which have been shown to be involved in cancer progression (Lu et al, 2005). Previous studies have shown that miRNAs can regulate glioma progression (Banelli et al, 2017;Shea et al, 2016), which makes miRNA a possible target for drug development in glioma. In the meanwhile, miRNAs and lncRNAs can also involve in the lncRNA-miRNA regulatory network to regulate cancer progression (Liz & Esteller, 2016 regulate renal carcinoma (Chiyomaru et al, 2013).…”

MiR‐16‐5p is frequently down‐regulated in astrocytic gliomas and modulates glioma cell proliferation, apoptosis and response to cytotoxic therapy

“…MiRNAs are small, noncoding RNAs that regulate gene expression preferentially by binding to the 3′‐untranslated region (3′‐UTR) of mRNAs in a sequence specific manner, thereby leading to inhibition of translation and/or enhanced mRNA degradation . Altered miRNA expression, including down‐regulation of tumour suppressive and up‐regulation of tumour promoting miRNAs, have been identified in many cancers , including gliomas . Among the first miRNAs implicated as tumour suppressors was miR‐16‐5p , which belongs to a family of evolutionary conserved miRNAs that share a common seed sequence.…”