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The microcosmos of cancer

Abstract

The discovery of microRNAs (miRNAs) almost two decades ago established a new paradigm of gene regulation. During the past ten years these tiny non-coding RNAs have been linked to virtually all known physiological and pathological processes, including cancer. In the same way as certain key protein-coding genes, miRNAs can be deregulated in cancer, in which they can function as a group to mark differentiation states or individually as bona fide oncogenes or tumour suppressors. Importantly, miRNA biology can be harnessed experimentally to investigate cancer phenotypes or used therapeutically as a target for drugs or as the drug itself.

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Figure 1: Mechanisms of miRNA perturbation in cancer.
Figure 2: Contribution of miRNAs to cancer pathways.
Figure 3: In vivo miRNA expression or inhibition 'á la carte'.
Figure 4: Proposed scheme for the treatment of liver cancer with combined chemotherapy and miRNA-based therapy.

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References

  1. Bartel, D. P. MicroRNAs: target recognition and regulatory functions. Cell 136, 215–233 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lee, R. C., Feinbaum, R. L. & Ambros, V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843–854 (1993).

    CAS  PubMed  Google Scholar 

  3. Wightman, B., Ha, I. & Ruvkun, G. Post-transcriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75, 855–862 (1993).

    CAS  PubMed  Google Scholar 

  4. Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646–674 (2011).

    CAS  PubMed  Google Scholar 

  5. 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). This article reports miRNA deregulation in cancer and is the first evidence of the role of miRNAs in cancer.

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  6. Lu, J. et al. MicroRNA expression profiles classify human cancers. Nature 435, 834–838 (2005). This article systematically profiles miRNAs in cancer and demonstrates their potential as classifiers.

    ADS  CAS  PubMed  Google Scholar 

  7. O'Donnell, K. A., Wentzel, E. A., Zeller, K. I., Dang, C. V. & Mendell, J. T. c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435, 839–843 (2005).

    ADS  CAS  PubMed  Google Scholar 

  8. He, L. et al. A microRNA polycistron as a potential human oncogene. Nature 435, 828–833 (2005). References 7 and 8 show, for the first time, that miRNAs can be actively involved in the MYC signalling pathway.

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  9. 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).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  10. Saito, Y. et al. Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells. Cancer Cell 9, 435–443 (2006).

    CAS  PubMed  Google Scholar 

  11. Mayr, C., Hemann, M. T. & Bartel, D. P. Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science 315, 1576–1579 (2007).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  12. Veronese, A. et al. Mutated β-catenin evades a microRNA-dependent regulatory loop. Proc. Natl Acad. Sci. USA 108, 4840–4845 (2011).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  13. Diederichs, S. & Haber, D. A. Sequence variations of microRNAs in human cancer: alterations in predicted secondary structure do not affect processing. Cancer Res. 66, 6097–6104 (2006).

    CAS  PubMed  Google Scholar 

  14. Kuchenbauer, F. et al. In-depth characterization of the microRNA transcriptome in a leukemia progression model. Genome Res. 18, 1787–1797 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Yanaihara, N. et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 9, 189–198 (2006).

    CAS  PubMed  Google Scholar 

  16. Calin, G. A. et al. A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N. Engl. J. Med. 353, 1793–1801 (2005).

    CAS  PubMed  Google Scholar 

  17. Rosenfeld, N. et al. MicroRNAs accurately identify cancer tissue origin. Nature Biotechnol. 26, 462–469 (2008).

    CAS  Google Scholar 

  18. Xi, Y. et al. Systematic analysis of microRNA expression of RNA extracted from fresh frozen and formalin-fixed paraffin-embedded samples. RNA 13, 1668–1674 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Mitchell, P. S. et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc. Natl Acad. Sci. USA 105, 10513–10518 (2008).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  20. Chang, T. C. et al. Widespread microRNA repression by Myc contributes to tumorigenesis. Nature Genet. 40, 43–50 (2008).

    CAS  PubMed  Google Scholar 

  21. Thomson, J. M. et al. Extensive post-transcriptional regulation of microRNAs and its implications for cancer. Genes Dev. 20, 2202–2207 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Kumar, M. S., Lu, J., Mercer, K. L., Golub, T. R. & Jacks, T. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nature Genet. 39, 673–677 (2007).

    CAS  PubMed  Google Scholar 

  23. Kumar, M. S. et al. Dicer1 functions as a haploinsufficient tumor suppressor. Genes Dev. 23, 2700–2704 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Merritt, W. M. et al. Dicer, Drosha, and outcomes in patients with ovarian cancer. N. Engl. J. Med. 359, 2641–2650 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Melo, S. A. et al. A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function. Nature Genet. 41, 365–370 (2009).

    CAS  PubMed  Google Scholar 

  26. Melo, S. A. et al. A genetic defect in exportin-5 traps precursor microRNAs in the nucleus of cancer cells. Cancer Cell 18, 303–315 (2010).

    CAS  PubMed  Google Scholar 

  27. Newman, M. A. & Hammond, S. M. Emerging paradigms of regulated microRNA processing. Genes Dev. 24, 1086–1092 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Mavrakis, K. J. et al. Genome-wide RNA-mediated interference screen identifies miR-19 targets in Notch-induced T-cell acute lymphoblastic leukaemia. Nature Cell Biol. 12, 372–379 (2010).

    CAS  PubMed  Google Scholar 

  29. Portela, A. & Esteller, M. Epigenetic modifications and human disease. Nature Biotechnol. 28, 1057–1068 (2010).

    CAS  Google Scholar 

  30. Cao, Q. et al. Coordinated regulation of Polycomb Group complexes through microRNAs in cancer. Cancer Cell 20, 187–199 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Fabbri, M. et al. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc. Natl Acad. Sci. USA 104, 15805–15810 (2007).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  32. Varambally, S. et al. Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer. Science 322, 1695–1699 (2008).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  33. Hwang, H. W., Wentzel, E. A. & Mendell, J. T. A hexanucleotide element directs microRNA nuclear import. Science 315, 97–100 (2007).

    ADS  CAS  PubMed  Google Scholar 

  34. Khraiwesh, B. et al. Transcriptional control of gene expression by microRNAs. Cell 140, 111–122 (2010).

    CAS  PubMed  Google Scholar 

  35. Gebeshuber, C. A., Zatloukal, K. & Martinez, J. miR-29a suppresses tristetraprolin, which is a regulator of epithelial polarity and metastasis. EMBO Rep. 10, 400–405 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Small, E. M. & Olson, E. N. Pervasive roles of microRNAs in cardiovascular biology. Nature 469, 336–342 (2011).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  37. Bueno, M. J. et al. Combinatorial effects of microRNAs to suppress the Myc oncogenic pathway. Blood 117, 6255–6266 (2011).

    CAS  PubMed  Google Scholar 

  38. Bui, T. V. & Mendell, J. T. Myc: maestro of microRNAs. Genes Cancer 1, 568–575 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Dews, M. et al. Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nature Genet. 38, 1060–1065 (2006).

    CAS  PubMed  Google Scholar 

  40. Cairo, S. et al. Stem cell-like micro-RNA signature driven by Myc in aggressive liver cancer. Proc. Natl Acad. Sci. USA 107, 20471–20476 (2010).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  41. Kent, O. A. et al. Repression of the miR-143/145 cluster by oncogenic Ras initiates a tumor-promoting feed-forward pathway. Genes Dev. 24, 2754–2759 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Johnson, S. M. et al. RAS is regulated by the let-7 microRNA family. Cell 120, 635–647 (2005). This article reports the first evidence of an oncogene, KRAS, being targeted by an miRNA.

    CAS  PubMed  Google Scholar 

  43. He, L., He, X., Lowe, S. W. & Hannon, G. J. microRNAs join the p53 network–another piece in the tumour-suppression puzzle. Nature Rev. Cancer 7, 819–822 (2007). This comprehensive review describes the regulation of the miR-34 family by the tumour suppressor p53.

    CAS  Google Scholar 

  44. Pichiorri, F. et al. Downregulation of p53-inducible microRNAs 192, 194, and 215 impairs the p53/MDM2 autoregulatory loop in multiple myeloma development. Cancer Cell 18, 367–381 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Xiao, J., Lin, H., Luo, X. & Wang, Z. miR-605 joins p53 network to form a p53:miR-605:Mdm2 positive feedback loop in response to stress. EMBO J. 30, 524–532 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Yamakuchi, M. et al. P53-induced microRNA-107 inhibits HIF-1 and tumor angiogenesis. Proc. Natl Acad. Sci. USA 107, 6334–6339 (2010).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  47. Chang, C. J. et al. p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs. Nature Cell Biol. 13, 317–323 (2011).

    CAS  PubMed  Google Scholar 

  48. Kim, T. et al. p53 regulates epithelial-mesenchymal transition through microRNAs targeting ZEB1 and ZEB2. J. Exp. Med. 208, 875–883 (2011).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  49. Swarbrick, A. et al. miR-380-5p represses p53 to control cellular survival and is associated with poor outcome in MYCN-amplified neuroblastoma. Nature Med. 16, 1134–1140 (2010).

    CAS  PubMed  Google Scholar 

  50. Hu, W. et al. Negative regulation of tumor suppressor p53 by microRNA miR-504. Mol. Cell 38, 689–699 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Suzuki, H. I. et al. Modulation of microRNA processing by p53. Nature 460, 529–533 (2009).

    ADS  CAS  PubMed  Google Scholar 

  52. Su, X. et al. TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs. Nature 467, 986–990 (2010).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ma, L., Teruya-Feldstein, J. & Weinberg, R. A. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449, 682–688 (2007). This study demonstrates for the first time that miRNAs are involved in tumour invasion and metastasis.

    ADS  CAS  PubMed  Google Scholar 

  54. Tavazoie, S. F. et al. Endogenous human microRNAs that suppress breast cancer metastasis. Nature 451, 147–152 (2008).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  55. Ma, L. et al. miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nature Cell Biol. 12, 247–256 (2010).

    CAS  PubMed  Google Scholar 

  56. Valastyan, S. et al. A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell 137, 1032–1046 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Cano, A. & Nieto, M. A. Non-coding RNAs take centre stage in epithelial-to-mesenchymal transition. Trends Cell Biol. 18, 357–359 (2008).

    CAS  PubMed  Google Scholar 

  58. Korpal, M. et al. Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nature Med. 17, 1101–1108 (2011).

    CAS  PubMed  Google Scholar 

  59. Martello, G. et al. A microRNA targeting Dicer for metastasis control. Cell 141, 1195–1207 (2010).

    CAS  PubMed  Google Scholar 

  60. Vander Heiden, M. G., Cantley, L. C. & Thompson, C. B. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324, 1029–1033 (2009).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  61. Godlewski, J. et al. MicroRNA-451 regulates LKB1/AMPK signaling and allows adaptation to metabolic stress in glioma cells. Mol. Cell 37, 620–632 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Gao, P. et al. c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 458, 762–765 (2009).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  63. Anand, S. et al. MicroRNA-132-mediated loss of p120RasGAP activates the endothelium to facilitate pathological angiogenesis. Nature Med. 16, 909–914 (2010).

    CAS  PubMed  Google Scholar 

  64. Mu, P. et al. Genetic dissection of the miR-1792 cluster of microRNAs in Myc-induced B-cell lymphomas. Genes Dev. 23, 2806–2811 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Olive, V. et al. miR-19 is a key oncogenic component of mir-17-92. Genes Dev. 23, 2839–2849 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Costinean, S. et al. Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)-miR155 transgenic mice. Proc. Natl Acad. Sci. USA 103, 7024–7029 (2006). This article reports overexpression of a single miRNA can cause cancer in vivo.

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  67. O'Connell, R. M. et al. Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder. J. Exp. Med. 205, 585–594 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Miska, E. A. et al. Most Caenorhabditis elegans microRNAs are individually not essential for development or viability. PLoS Genet. 3, e215 (2007).

    PubMed  PubMed Central  Google Scholar 

  69. Klein, U. et al. The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia. Cancer Cell 17, 28–40 (2010).

    CAS  PubMed  Google Scholar 

  70. Medina, P. P., Nolde, M. & Slack, F. J. OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma. Nature 467, 86–90 (2010).

    ADS  CAS  PubMed  Google Scholar 

  71. Chan, J. A., Krichevsky, A. M. & Kosik, K. S. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 65, 6029–6033 (2005).

    CAS  PubMed  Google Scholar 

  72. Prosser, H. M., Koike-Yusa, H., Cooper, J. D., Law, F. C. & Bradley, A. A resource of vectors and ES cells for targeted deletion of microRNAs in mice. Nature Biotechnol. 29, 840–845 (2011).

    CAS  Google Scholar 

  73. Loya, C. M., Lu, C. S., Van Vactor, D. & Fulga, T. A. Transgenic microRNA inhibition with spatiotemporal specificity in intact organisms. Nature Methods 6, 897–903 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Zhu, Q. et al. A sponge transgenic mouse model reveals important roles for the miRNA-183/96/182 cluster in post-mitotic photoreceptors of the retina. J. Biol. Chem. 2865, 31749–31760 (2011). This article reports the development of the first sponge transgenic mouse that allows in vivo inhibition of one or several miRNAs.

    Google Scholar 

  75. Kota, J. et al. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell 137, 1005–1017 (2009). This article uses adenovirus-associated vectors to deliver miRNAs to the liver and treat cancer.

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Czech, B. & Hannon, G. J. Small RNA sorting: matchmaking for Argonautes. Nature Rev. Genet. 12, 19–31 (2011).

    CAS  PubMed  Google Scholar 

  77. Chicas, A. et al. Dissecting the unique role of the retinoblastoma tumor suppressor during cellular senescence. Cancer Cell 17, 376–387 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Stegmeier, F., Hu, G., Rickles, R. J., Hannon, G. J. & Elledge, S. J. A lentiviral microRNA-based system for single-copy polymerase II-regulated RNA interference in mammalian cells. Proc. Natl Acad. Sci. USA 102, 13212–13217 (2005).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  79. Zuber, J. et al. Toolkit for evaluating genes required for proliferation and survival using tetracycline-regulated RNAi. Nature Biotechnol. 29, 79–83 (2010).

    Google Scholar 

  80. Fellmann, C. et al. Functional identification of optimized RNAi triggers using a massively parallel sensor assay. Mol. Cell 41, 733–746 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Premsrirut, P. K. et al. A rapid and scalable system for studying gene function in mice using conditional RNA interference. Cell 145, 145–158 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Seibler, J. et al. Reversible gene knockdown in mice using a tight, inducible shRNA expression system. Nucleic. Acids Res. 35, e54 (2007).

    PubMed  PubMed Central  Google Scholar 

  83. 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).

    CAS  PubMed  Google Scholar 

  84. Zender, L. et al. An oncogenomics-based in vivo RNAi screen identifies tumor suppressors in liver cancer. Cell 135, 852–864 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Westbrook, T. F. et al. A genetic screen for candidate tumor suppressors identifies REST. Cell 121, 837–848 (2005).

    CAS  PubMed  Google Scholar 

  86. Xue, W. et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 445, 656–660 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Luo, J. et al. A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene. Cell 137, 835–848 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Scholl, C. et al. Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells. Cell 137, 821–834 (2009).

    CAS  PubMed  Google Scholar 

  89. Barbie, D. A. et al. Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature 462, 108–112 (2009).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  90. Zuber, J. et al. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature 478, 524–528 (2011).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  91. Gumireddy, K. et al. Small-molecule inhibitors of microRNA miR-21 function. Angew. Chem. Int. Ed. Engl. 47, 7482–7484 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Melo, S. et al. Small molecule enoxacin is a cancer-specific growth inhibitor that acts by enhancing TAR RNA-binding protein 2-mediated microRNA processing. Proc. Natl. Acad. Sci. USA 108, 4394–4399 (2011).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  93. Garzon, R., Marcucci, G. & Croce, C. M. Targeting microRNAs in cancer: rationale, strategies and challenges. Nature Rev. Drug Discov. 9, 775–789 (2010).

    CAS  Google Scholar 

  94. Lanford, R. E. et al. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 327, 198–201 (2009).

    ADS  PubMed  PubMed Central  Google Scholar 

  95. Obad, S. et al. Silencing of microRNA families by seed-targeting tiny LNAs. Nature Genet. 43, 371–378 (2011).

    CAS  PubMed  Google Scholar 

  96. Bonci, D. et al. The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nature Med. 14, 1271–1277 (2008).

    CAS  PubMed  Google Scholar 

  97. Kumar, M. S. et al. Suppression of non-small cell lung tumor development by the let-7 microRNA family. Proc. Natl Acad. Sci. USA 105, 3903–3908 (2008).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  98. Poliseno, L. et al. A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 465, 1033–1038 (2010). This elegant study shows how mRNA from genes and pseudogenes can compete for the binding of miRNAs, unveiling the complexity of miRNA regulatory networks.

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  99. Ruby, J. G., Jan, C. H. & Bartel, D. P. Intronic microRNA precursors that bypass Drosha processing. Nature 448, 83–86 (2007).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  100. Cheloufi, S., Dos Santos, C. O., Chong, M. M. & Hannon, G. J. A dicer-independent miRNA biogenesis pathway that requires Ago catalysis. Nature 465, 584–589 (2010).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We apologize to all colleagues whose work could not be cited owing to space restrictions. We thank L. Dow, A. Ventura, A. Saborowski and V. Aranda for their comments on the manuscript, and G. Hannon and L. He for the many discussions. A.L. is supported by an EMBO Long-Term Fellowship. S.W.L. is a Howard Hughes Medical Institute investigator.

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Lujambio, A., Lowe, S. The microcosmos of cancer. Nature 482, 347–355 (2012). https://doi.org/10.1038/nature10888

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