A microRNA polycistron as a potential human oncogene

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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.


  1. 1

    Ota, A. et al. Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma. Cancer Res. 64, 3087–3095 (2004)

  2. 2

    Lee, Y. et al. The nuclear RNase III Drosha initiates microRNA processing. Nature 425, 415–419 (2003)

  3. 3

    Bernstein, E., Caudy, A. A., Hammond, S. M. & Hannon, G. J. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409, 363–366 (2001)

  4. 4

    Bartel, D. P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281–297 (2004)

  5. 5

    Ambros, V. The functions of animal microRNAs. Nature 431, 350–355 (2004)

  6. 6

    He, L. & Hannon, G. J. MicroRNAs: small RNAs with a big role in gene regulation. Nature Rev. Genet. 5, 522–531 (2004)

  7. 7

    Ruvkun, G. & Giusto, J. The Caenorhabditis elegans heterochronic gene lin-14 encodes a nuclear protein that forms a temporal developmental switch. Nature 338, 313–319 (1989)

  8. 8

    Ambros, V. A hierarchy of regulatory genes controls a larva-to-adult developmental switch in C. elegans. Cell 57, 49–57 (1989)

  9. 9

    Chang, S., Johnston, R. J. Jr, Frokjaer-Jensen, C., Lockery, S. & Hobert, O. MicroRNAs act sequentially and asymmetrically to control chemosensory laterality in the nematode. Nature 430, 785–789 (2004)

  10. 10

    Johnston, R. J. & Hobert, O. A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans. Nature 426, 845–849 (2003)

  11. 11

    Brennecke, J., Hipfner, D. R., Stark, A., Russell, R. B. & Cohen, S. M. bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell 113, 25–36 (2003)

  12. 12

    Chen, C. Z., Li, L., Lodish, H. F. & Bartel, D. P. MicroRNAs modulate hematopoietic lineage differentiation. Science 303, 83–86 (2004)

  13. 13

    Knuutila, S. et al. DNA copy number amplifications in human neoplasms: review of comparative genomic hybridization studies. Am. J. Pathol. 152, 1107–1123 (1998)

  14. 14

    Tanzer, A. & Stadler, P. F. Molecular evolution of a microRNA cluster. J. Mol. Biol. 339, 327–335 (2004)

  15. 15

    Tusher, V. G., Tibshirani, R. & Chu, G. Significance analysis of microarrays applied to the ionizing radiation response. Proc. Natl Acad. Sci. USA 98, 5116–5121 (2001)

  16. 16

    Adams, J. M. et al. The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature 318, 533–538 (1985)

  17. 17

    Schmitt, C. A. et al. Dissecting p53 tumor suppressor functions in vivo. Cancer Cell 1, 289–298 (2002)

  18. 18

    Hemann, M. T. et al. An epi-allelic series of p53 hypomorphs created by stable RNAi produces distinct tumor phenotypes in vivo. Nature Genet. 33, 396–400 (2003)

  19. 19

    Hemann, M. T. et al. Suppression of tumorigenesis by the p53 target PUMA. Proc. Natl Acad. Sci. USA 101, 9333–9338 (2004)

  20. 20

    Wendel, H. G. et al. Survival signalling by Akt and eIF4E in oncogenesis and cancer therapy. Nature 428, 332–337 (2004)

  21. 21

    Thomson, J. M., Parker, J., Perou, C. M. & Hammond, S. M. A custom microarray plateform for analysis of microRNA gene expression. Nature Methods 1, 47–53 (2004)

  22. 22

    Calin, G. A. et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc. Natl Acad. Sci. USA 101, 2999–3004 (2004)

  23. 23

    Calin, G. A. et al. MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc. Natl Acad. Sci. USA 101, 11755–11760 (2004)

  24. 24

    Metzler, M., Wilda, M., Busch, K., Viehmann, S. & Borkhardt, A. High expression of precursor microRNA-155/BIC RNA in children with Burkitt lymphoma. Genes Chromosom. Cancer 39, 167–169 (2004)

  25. 25

    Michael, M. Z., O'Connor, S. M., van Holst Pellekaan, N. G., Young, G. P. & James, R. J. Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol. Cancer Res. 1, 882–891 (2003)

  26. 26

    Calin, G. A. et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc. Natl Acad. Sci. USA 99, 15524–15529 (2002)

  27. 27

    Di Cristofano, A., De Acetis, M., Koff, A., Cordon-Cardo, C. & Pandolfi, P. P. Pten and p27KIP1 cooperate in prostate cancer tumor suppression in the mouse. Nature Genet. 27, 222–224 (2001)

  28. 28

    Mayor, C. et al. VISTA: visualizing global DNA sequence alignments of arbitrary length. Bioinformatics 16, 1046–1047 (2000)

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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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