A microRNA polycistron as a potential human oncogene

Abstract

MicroRNAs are regulatory, non-coding RNAs about 22 nucleotides in length: over 200 have been identified in humans, and their functions are beginning to be pinned down. It has been suggested that like other regulatory molecules they might be involved in tumour formation, and three papers in this issue confirm that this is the case. One cluster of microRNAs, known as mir-17–92, is shown to be a potential oncogene by its action in an in vivo model of human B-cell lymphoma. A cluster of microRNAs on human chromosome 13 has been found to be regulated by c-Myc, an important transcription factor that is overexpressed in many human cancers. And analysis of microRNA expression in over 300 individuals shows that microRNA profiles could be of value in cancer diagnosis. There is a global downregulation of microRNA in tumours, and the microRNA profile also reflects the origin and differentiation state of the tumours. To date, more than 200 microRNAs have been described in humans; however, the precise functions of these regulatory, non-coding RNAs remains largely obscure. One cluster of microRNAs, the mir-17–92 polycistron, is located in a region of DNA that is amplified in human B-cell lymphomas1. Here we compared B-cell lymphoma samples and cell lines to normal tissues, and found that the levels of the primary or mature microRNAs derived from the mir-17–92 locus are often substantially increased in these cancers. Enforced expression of the mir-17–92 cluster acted with c-myc expression to accelerate tumour development in a mouse B-cell lymphoma model. Tumours derived from haematopoietic stem cells expressing a subset of the mir-17–92 cluster and c-myc could be distinguished by an absence of apoptosis that was otherwise prevalent in c-myc-induced lymphomas. Together, these studies indicate that non-coding RNAs, specifically microRNAs, can modulate tumour formation, and implicate the mir-17–92 cluster as a potential human oncogene.