Clinical implications of microRNAs in human glioblastoma

Abstract

Glioblastoma (GBM) is one of the most common and dismal brain tumors in adults. Further elucidation of the molecular pathogenesis of GBM is mandatory to improve the overall survival of patients. A novel small non-coding RNA molecule, microRNA (miRNA), appears to represent one of the most attractive target molecules contributing to the pathogenesis of various types of tumors. Recent global analyses have revealed that several miRNAs are clinically implicated in GBM, with some reports indicating the association of miRNA dysregulation with acquired temozolomide (TMZ) resistance. More recent studies have revealed that miRNAs could play a role in cancer stem cell (CSC) properties, contributing to treatment resistance. In addition, greater impact might be expected from miRNA-targeted therapies based on tumor-derived exosomes that contain numerous functional miRNAs, which could be transferred between tumor cells and surrounding structures. Tumor-derived miRNAs are now considered to be a novel molecular mechanism promoting the progression of GBM. Establishment of miRNA-targeted therapies based on miRNA dysregulation of CSCs could provide effective therapeutic strategies for TMZ-resistant GBM. Recent progress has revealed that miRNAs are not only putative biological markers for diagnosis, but also one of the most promising targets for GBM treatment. Here in, we summarize the translational aspects of miRNAs in the diagnosis and treatment of GBM.

Keywords: exosome; glioblastoma; microRNA; temozolomide.

FIGURE 1

Concept of microRNA-targeted therapy. Expression of target genes is negatively regulated by microRNA (miRNA) via mRNA cleavage or translational inhibition. Therefore, miRNA acts as oncogenic miRNA when the target genes are tumor suppressor genes, and as tumor-suppressive miRNA when the target genes are oncogenes. Through regulation of tumor-related genes, miRNA could activate specific signaling pathways. A single miRNA could regulate expression of multiple genes, so the functions of miRNA are varied, affecting cancer stem cell properties, tumor proliferation, apoptosis, invasion, and angiogenesis. miRNA has the potential to play roles in tumorigenesis, malignant transformation, and treatment resistance. Theoretically, there are two approaches to miRNA-targeted therapy: inhibition of oncogenic miRNA with antago-miRs; and replacement of tumor-suppressive miRNA with miRNA mimics.