miRNA regulation in Gliomas: Usual suspects in glial tumorigenesis and evolving clinical applications

Abstract

In recent years, an increasing role for noncoding small RNAs (miRNA) has been uncovered in carcinogenesis. These oligonucleotides can promote degradation and/or inhibit translation of key mRNAs. Recent studies have also highlighted a possible role for miRNAs in adult and pediatric brain tumors, including high- and low-grade gliomas, medulloblastoma, ependymoma, and neoplasms associated with neurofibromatosis type 1. Gliomas represent the most common category of primary intraparenchymal brain tumors, and, for example, manipulation of signaling pathways, through inhibition of PTEN transcription appears to be an important function of miRNA dysregulation through miR-21, miR-106b, and miR-26a. Moreover, altered miRNA expression in gliomas play roles in the regulation of common tumorigenic processes, including receptor tyrosine kinase signaling, angiogenesis, invasion, suppression of differentiation, cell cycle enhancement, and inhibition of apoptosis. Suppression of differentiation requires the downregulation of a number of miRNAs that are both enriched in the brain and required for terminal glial differentiation, including miR-219 and miR-338. Our evolving understanding about the biology of gliomas make them attractive for miRNA study, given that recent evidence suggests that epigenetic and subtle genetic changes may contribute to their pathogenesis. Identification of key miRNAs also provides a rationale for developing robust biomarkers and inhibitory RNA strategies for therapeutic purposes in glioma patients.