A microRNA Polycistron as a Potential Human Oncogene

Nature. 2005 Jun 9;435(7043):828-33. doi: 10.1038/nature03552.

Abstract

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 lymphomas. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Disease Models, Animal
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Genes / genetics*
  • Genes, myc / genetics
  • Humans
  • Lymphoma, B-Cell* / genetics*
  • Mice
  • MicroRNAs / genetics*
  • Molecular Sequence Data
  • Multigene Family / genetics
  • Oncogenes / genetics*
  • Phenotype
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • MicroRNAs
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger

Associated data

  • GENBANK/GSM45026
  • GENBANK/GSM45027
  • GENBANK/GSM45028
  • GENBANK/GSM45029
  • GENBANK/GSM45030
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  • GENBANK/GSM45063
  • GENBANK/GSM45064
  • GENBANK/GSM45065