Mir-17-92, a cluster of miRNAs in the midst of the cancer network

Abstract

MicroRNAs (miRNAs) are an abundant class of small non-coding RNAs (ncRNAs) that function to regulate gene expression at the post-transcriptional level. Although their functions were originally described during normal development, miRNAs have emerged as integral components of the oncogenic and tumor suppressor network, regulating nearly all cellular processes altered during tumor formation. In particular, mir-17-92, a miRNA polycistron also known as oncomir-1, is among the most potent oncogenic miRNAs. Genomic amplification and elevated expression of mir-17-92 were both found in several human B-cell lymphomas, and its enforced expression exhibits strong tumorigenic activity in multiple mouse tumor models. mir-17-92 carries out pleiotropic functions during both normal development and malignant transformation, as it acts to promote proliferation, inhibit differentiation, increase angiogenesis, and sustain cell survival. Unlike most protein coding genes, mir-17-92 is a polycistronic miRNA cluster that contains multiple miRNA components, each of which has a potential to regulate hundreds of target mRNAs. This unique gene structure of mir-17-92 may underlie the molecular basis for its pleiotropic functions in a cell type- and context-dependent manner. Here we review the recent literature on the functional studies of mir-17-92 and highlight its potential impacts on the oncogene network. These findings on mir-17-92 indicate that miRNAs are integrated components of the molecular pathways that regulate tumor development and tumor maintenance.