A role for the cancer-associated miR-106b~25 cluster in neuronal stem cells

the last decade, micro-RNAs (miRNAs) have emerged as major regulators of cell fate. They are involved in fine-tuning gene expression in normal developing tissues and are often aberrantly expressed in different disease states, including cancer. miRNAs are 20-25 nucleotide non-coding RNAs that repress the translation and stability of a large number of target mRNAs. The study by Brett et al in the previous issue of AGING adds to our understanding of how miRNAs regulate the differentiation of adult neural stem cells (NSCs) [1]. The authors used primary cultures of neural stem/progenitor cells (NSPCs) isolated from adult mice to investigate the importance of a specific miRNA cluster, miR-106b~25, in regulating the proliferative potential and differentiation of NSCs. This miRNA cluster is located within an intronic region of the Mcm7 gene and codes for three different miRNA species, miR-106b, miR-93 and miR-25. Interestingly, activation of this miRNA cluster has been observed in different tumour types and is involved in the inhibition of anti-proliferative and pro-apoptotic genes, such as p21, Bim and TGF-beta [2,3]. Furthermore, this cluster is overexpressed in prostate cancer where it is involved in the downregulation of PTEN expression and also cooperates with its host gene Mcm7 to drive tumourigenesis [4]. The current study shows that the miR-106b~25 cluster is present in self-renewing adult NSPCs and does not change its expression when cells are stimulated to undergo differentiation. Among the three miRNAs within the cluster, miR-25 seems to be the most impor-Commentary tant for maintaining proliferation of adult NSPC. Overexpression of either miR-25, or the whole cluster, induced proliferation of NSPCs and increased the proportion of cells positive for the neuronal marker Tuj1. Micro-RNAs are key regulators of proliferation, self-renewal and differentiation in both embryonic and adult stem cells [5]. Embryonic stem cells deplete of Dicer, an essential component of the miRNA processing machinery, fail to induce a differentiation marker upon induction of differentiation in vitro [6]. miRNAs are also involved in fine-tuning gene expression during the transition of neuronal stem cells to neuronal progenitors and neurons [7]. Some of the target genes of miRNAs involved in neurogenesis have been identified, but a large component of the complex regulatory networks, involving both positive and negative feedback loops, remains to be elucidated. Brett et al. used a bioinformatics approach to identify potential targets of miR-25 and found over-representation of genes involved in the TGF-beta and insulin/IGF/Akt signalling pathways. The insulin/IGF/Akt signalling …