A microRNA polycistron as a potential human oncogene

He, Lin
Thomson, J. Michael
Hemann, Michael T.
Hernando-Monge, Eva
Mu, David
Goodson, Summer
Powers, Scott
Cordon-Cardo, Carlos
Lowe, Scott W.
Hannon, Gregory J.
Hammond, Scott M.

¹Cold Spring Harbor Laboratory, Watson School of Biological Sciences, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA. ²Department of Cell and Developmental Biology and ³Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA. ⁴Memorial Sloan-Kettering Cancer Center, Division of Molecular Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, New York 10021, USA.

doi:10.1038/nature03552

*These authors contributed equally to this work.

Received 15 February; accepted 16 March 2005.

Supplementary Information is linked to the online version of the paper at www.nature.com/nature.

Author Information Microarray data have been deposited in NCBI-GEO under accession numbers GSM45026-GSM45065 and GSE-2399. Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests. Correspondence and requests for materials should be addressed to G.J.H. ([email protected]) or S.M.H. ([email protected]).

Nature 435(7043):p 828-833, June 9, 2005.

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, themir-17-92polycistron, 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 themir-17-92locus are often substantially increased in these cancers. Enforced expression of themir-17-92cluster acted withc-mycexpression to accelerate tumour development in a mouse B-cell lymphoma model. Tumours derived from haematopoietic stem cells expressing a subset of themir-17-92cluster andc-myccould be distinguished by an absence of apoptosis that was otherwise prevalent inc-myc-induced lymphomas. Together, these studies indicate that non-coding RNAs, specifically microRNAs, can modulate tumour formation, and implicate themir-17-92cluster as a potential human oncogene.