A microRNA polycistron as a potential human oncogene

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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-1792 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-1792 locus are often substantially increased in these cancers. Enforced expression of the mir-1792 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-1792 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-1792 cluster as a potential human oncogene.

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Figure 1: The mir-17 92 cluster shows increased expression in B-cell lymphoma samples and cell lines.
Figure 2: Overexpression of the mir-17 19b cluster accelerates c-myc -induced lymphomagenesis in mice.
Figure 3: Pathological and immunological analysis of lymphomas produced by cooperation between mir-17 19b and c-myc.

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Acknowledgements

We thank members of the Hannon, Lowe and Hammond laboratories for discussions and input. We also thank Z. Xuan, N. Chen, N. Sheth and R. Sachidanandam for bioniformatic analysis. C. Perou and J. Leib provided advice and support for microarray methodologies, and A. Barnes and B. Boone gave assistance with mouse tissue procurement. We are grateful to H. Wendel, C. Scott, C. Marsden and C. Rosenthal, R. Karni, P. Moody and R. Whitaker, who provided advice and technical support. F. Slack coined the oncomiR nomenclature. L.H. and M.T.H. are Fellows of the Helen Hay Whitney Foundation. S.W.L. and C.C.-C. are supported by a program project grant from the NCI. G.J.H is supported by an Innovator Award from the US Army Breast Cancer Research Program and by grants from the DOD and NIH. S.M.H. is a General Motors Cancer Research Foundation Scholar, and J.M.T is a Frederick Gardner Cottrell Postdoctoral Fellow.

Author information

Correspondence to Gregory J. Hannon or Scott M. Hammond.

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Competing interests

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.

Supplementary information

Supplementary Figure S1

Full cluster analysis of miRNA expression patterns in cell lines shown to carry the chromosome 13 amplicon. (PDF 275 kb)

Supplementary Figure S2

Comparison of expression of miRNAs from the mir17-92 cluster in Eµ-myc/mir17-19b tumors to Eµ-myc tumors and Karpas cells. (PDF 169 kb)

Supplementary Table S1

Full output of SAM analysis for cell line microarrays. (PDF 99 kb)

Supplementary Table S2

List of individual microRNAs tested for acceleration of Eµ-myc lymphomas. (PDF 111 kb)

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He, L., Thomson, J., Hemann, M. et al. A microRNA polycistron as a potential human oncogene. Nature 435, 828–833 (2005) doi:10.1038/nature03552

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