miR miR on the wall, who's the most malignant medulloblastoma miR of them all?

Abstract

microRNAs (miRNAs) have wide-ranging effects on large-scale gene regulation. As such, they play a vital role in dictating normal development, and their aberrant expression has been implicated in cancer. There has been a large body of research on the role of miRNAs in medulloblastoma, the most common malignant brain tumor of childhood. The identification of the 4 molecular subgroups with distinct biological, genetic, and transcriptional features has revolutionized the field of medulloblastoma research over the past 5 years. Despite this, the growing body of research on miRNAs in medulloblastoma has largely focused on the clinical entity of a single disease rather than the molecular subgroups. This review begins by highlighting the role of miRNAs in development and progresses to explore their myriad of implications in cancer. Medulloblastoma is characterized by increased proliferation, inhibition of apoptosis, and maintenance of stemness programs-features that are inadvertently regulated by altered expression patterns in miRNAs. This review aims to contextualize the large body of work on miRNAs within the framework of medulloblastoma subgroups. The goal of this review is to stimulate new areas of research, including potential therapeutics, within a rapidly growing field.

Fig. 1

Dichotomous roles of miR-34a, miR-9, and miR-124 in normal neuronal development and medulloblastoma. In normal neurons, activation of differentiation programs induces miRNAs to repress cell cycle progression. In medulloblastoma, repression of several miRNAs, including miR-34a, miR-9, and miR-124, leads to unregulated cell proliferation. Inhibition of p53 leads to silencing of p21 and miR-34a, which allows cell cycle progression. Expression of REST inhibits proneuronal differentiation miRNAs miR-9 and miR-124.