Cancer and Metastasis Reviews

, Volume 37, Issue 1, pp 5–15 | Cite as

MicroRNAs and metastasis: small RNAs play big roles

  • Jongchan Kim
  • Fan Yao
  • Zhenna Xiao
  • Yutong SunEmail author
  • Li MaEmail author


MicroRNAs (miRNAs) are small non-coding RNAs regulating post-transcriptional gene expression. They play important roles in many biological processes under physiological or pathological conditions, including development, metabolism, tumorigenesis, metastasis, and immune response. Over the past 15 years, significant insights have been gained into the roles of miRNAs in cancer. Depending on the cancer type, miRNAs can act as oncogenes, tumor suppressors, or metastasis regulators. In this review, we focus on the role of miRNAs as components of molecular networks regulating metastasis. These miRNAs, termed metastamiRs, promote or inhibit metastasis through various mechanisms, including regulation of migration, invasion, colonization, cancer stem cell properties, epithelial-mesenchymal transition, and microenvironment. Some of these metastamiRs represent attractive therapeutic targets for cancer treatment.


MicroRNA (miRNA) OncomiR MetastamiR Metastasis 



We thank Baochau Ton for critical reading of the manuscript. The authors’ research is supported by the US National Institutes of Health grants R01CA166051 and R01CA181029, a Cancer Prevention and Research Institute of Texas grant RP150319, and a Stand Up To Cancer Innovative Research Grant.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Bartel, D. P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116(2), 281–297.PubMedCrossRefGoogle Scholar
  2. 2.
    Winter, J., Jung, S., Keller, S., Gregory, R. I., & Diederichs, S. (2009). Many roads to maturity: microRNA biogenesis pathways and their regulation. Nature Cell Biology, 11(3), 228–234.PubMedCrossRefGoogle Scholar
  3. 3.
    Gregory, R. I., Yan, K. P., Amuthan, G., Chendrimada, T., Doratotaj, B., Cooch, N., et al. (2004). The microprocessor complex mediates the genesis of microRNAs. Nature, 432(7014), 235–240.PubMedCrossRefGoogle Scholar
  4. 4.
    Han, J., Lee, Y., Yeom, K. H., Kim, Y. K., Jin, H., & Kim, V. N. (2004). The Drosha-DGCR8 complex in primary microRNA processing. Genes & Development, 18(24), 3016–3027.CrossRefGoogle Scholar
  5. 5.
    Han, J., Lee, Y., Yeom, K. H., Nam, J. W., Heo, I., Rhee, J. K., et al. (2006). Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell, 125(5), 887–901.PubMedCrossRefGoogle Scholar
  6. 6.
    Lund, E., Guttinger, S., Calado, A., Dahlberg, J. E., & Kutay, U. (2004). Nuclear export of microRNA precursors. Science, 303(5654), 95–98.PubMedCrossRefGoogle Scholar
  7. 7.
    Yi, R., Qin, Y., Macara, I. G., & Cullen, B. R. (2003). Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes & Development, 17(24), 3011–3016.CrossRefGoogle Scholar
  8. 8.
    Bohnsack, M. T., Czaplinski, K., & Gorlich, D. (2004). Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA, 10(2), 185–191.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Ha, M., & Kim, V. N. (2014). Regulation of microRNA biogenesis. Nature Reviews. Molecular Cell Biology, 15(8), 509–524.PubMedCrossRefGoogle Scholar
  10. 10.
    Lin, S., & Gregory, R. I. (2015). MicroRNA biogenesis pathways in cancer. Nature Reviews. Cancer, 15(6), 321–333.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Eichhorn, S. W., Guo, H., McGeary, S. E., Rodriguez-Mias, R. A., Shin, C., Baek, D., et al. (2014). mRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues. Molecular Cell, 56(1), 104–115.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Guo, H., Ingolia, N. T., Weissman, J. S., & Bartel, D. P. (2010). Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature, 466(7308), 835–840.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Ambros, V. (2004). The functions of animal microRNAs. Nature, 431(7006), 350–355.PubMedCrossRefGoogle Scholar
  14. 14.
    Massart, J., Katayama, M., & Krook, A. (2016). Micromanaging glucose and lipid metabolism in skeletal muscle: role of microRNAs. Biochimica et Biophysica Acta, 1861(12 Pt B), 2130–2138.PubMedCrossRefGoogle Scholar
  15. 15.
    Rupaimoole, R., & Slack, F. J. (2017). MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nature Reviews. Drug Discovery, 16(3), 203–222.PubMedCrossRefGoogle Scholar
  16. 16.
    Ma, L. (2016). MicroRNA and metastasis. Advances in Cancer Research, 132, 165–207.PubMedCrossRefGoogle Scholar
  17. 17.
    Pencheva, N., & Tavazoie, S. F. (2013). Control of metastatic progression by microRNA regulatory networks. Nature Cell Biology, 15(6), 546–554.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Trobaugh, D. W., & Klimstra, W. B. (2017). MicroRNA regulation of RNA virus replication and pathogenesis. Trends in Molecular Medicine, 23(1), 80–93.PubMedCrossRefGoogle Scholar
  19. 19.
    Xiao, C., & Rajewsky, K. (2009). MicroRNA control in the immune system: basic principles. Cell, 136(1), 26–36.PubMedCrossRefGoogle Scholar
  20. 20.
    Ling, H., Fabbri, M., & Calin, G. A. (2013). MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nature Reviews. Drug Discovery, 12(11), 847–865.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Calin, G. A., Dumitru, C. D., Shimizu, M., Bichi, R., Zupo, S., Noch, E., et al. (2002). Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proceedings of the National Academy of Sciences of the United States of America, 99(24), 15524–15529.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Klein, U., Lia, M., Crespo, M., Siegel, R., Shen, Q., Mo, T., et al. (2010). The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia. Cancer Cell, 17(1), 28–40.PubMedCrossRefGoogle Scholar
  23. 23.
    Lu, J., Getz, G., Miska, E. A., Alvarez-Saavedra, E., Lamb, J., Peck, D., et al. (2005). MicroRNA expression profiles classify human cancers. Nature, 435(7043), 834–838.PubMedCrossRefGoogle Scholar
  24. 24.
    He, L., Thomson, J. M., Hemann, M. T., Hernando-Monge, E., Mu, D., Goodson, S., et al. (2005). A microRNA polycistron as a potential human oncogene. Nature, 435(7043), 828–833.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Xiao, C., Srinivasan, L., Calado, D. P., Patterson, H. C., Zhang, B., Wang, J., et al. (2008). Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nature Immunology, 9(4), 405–414.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Krichevsky, A. M., & Gabriely, G. (2009). MiR-21: a small multi-faceted RNA. Journal of Cellular and Molecular Medicine, 13(1), 39–53.PubMedCrossRefGoogle Scholar
  27. 27.
    Hatley, M. E., Patrick, D. M., Garcia, M. R., Richardson, J. A., Bassel-Duby, R., van Rooij, E., et al. (2010). Modulation of K-Ras-dependent lung tumorigenesis by MicroRNA-21. Cancer Cell, 18(3), 282–293.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Medina, P. P., Nolde, M., & Slack, F. J. (2010). OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma. Nature, 467(7311), 86–90.PubMedCrossRefGoogle Scholar
  29. 29.
    Pasquinelli, A. E., Reinhart, B. J., Slack, F., Martindale, M. Q., Kuroda, M. I., Maller, B., et al. (2000). Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature, 408(6808), 86–89.PubMedCrossRefGoogle Scholar
  30. 30.
    Balzeau, J., Menezes, M. R., Cao, S., & Hagan, J. P. (2017). The LIN28/let-7 pathway in cancer. Frontiers in Genetics, 8, 31.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Johnson, S. M., Grosshans, H., Shingara, J., Byrom, M., Jarvis, R., Cheng, A., et al. (2005). RAS is regulated by the let-7 microRNA family. Cell, 120(5), 635–647.PubMedCrossRefGoogle Scholar
  32. 32.
    Esquela-Kerscher, A., Trang, P., Wiggins, J. F., Patrawala, L., Cheng, A., Ford, L., et al. (2008). The let-7 microRNA reduces tumor growth in mouse models of lung cancer. Cell Cycle, 7(6), 759–764.PubMedCrossRefGoogle Scholar
  33. 33.
    He, X., He, L., & Hannon, G. J. (2007). The guardian’s little helper: microRNAs in the p53 tumor suppressor network. Cancer Research, 67(23), 11099–11101.PubMedCrossRefGoogle Scholar
  34. 34.
    He, L., He, X., Lim, L. P., de Stanchina, E., Xuan, Z., Liang, Y., et al. (2007). A microRNA component of the p53 tumour suppressor network. Nature, 447(7148), 1130–1134.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Concepcion, C. P., Han, Y. C., Mu, P., Bonetti, C., Yao, E., D'Andrea, A., et al. (2012). Intact p53-dependent responses in miR-34-deficient mice. PLoS Genetics, 8(7), e1002797.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Cheng, C. Y., Hwang, C. I., Corney, D. C., Flesken-Nikitin, A., Jiang, L., Oner, G. M., et al. (2014). MiR-34 cooperates with p53 in suppression of prostate cancer by joint regulation of stem cell compartment. Cell Reports, 6(6), 1000–1007.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Brabletz, T., Lyden, D., Steeg, P. S., & Werb, Z. (2013). Roadblocks to translational advances on metastasis research. Nature Medicine, 19(9), 1104–1109.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Wan, L., Pantel, K., & Kang, Y. (2013). Tumor metastasis: moving new biological insights into the clinic. Nature Medicine, 19(11), 1450–1464.PubMedCrossRefGoogle Scholar
  39. 39.
    Eccles, S. A., & Welch, D. R. (2007). Metastasis: recent discoveries and novel treatment strategies. Lancet, 369(9574), 1742–1757.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Talmadge, J. E., & Fidler, I. J. (2010). AACR centennial series: the biology of cancer metastasis: historical perspective. Cancer Research, 70(14), 5649–5669.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Steeg, P. S. (2012). Perspective: the right trials. Nature, 485(7400), S58–S59.PubMedCrossRefGoogle Scholar
  42. 42.
    Sun, Y., & Ma, L. (2015). The emerging molecular machinery and therapeutic targets of metastasis. Trends in Pharmacological Sciences, 36(6), 349–359.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Ma, L., Teruya-Feldstein, J., & Weinberg, R. A. (2007). Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature, 449(7163), 682–688.PubMedCrossRefGoogle Scholar
  44. 44.
    Ma, L., Reinhardt, F., Pan, E., Soutschek, J., Bhat, B., Marcusson, E. G., et al. (2010). Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model. Nature Biotechnology, 28(4), 341–347.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Ma, L. (2010). Role of miR-10b in breast cancer metastasis. Breast Cancer Research, 12(5), 210.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Yoo, B., Kavishwar, A., Ross, A., Wang, P., Tabassum, D. P., Polyak, K., et al. (2015). Combining miR-10b-targeted nanotherapy with low-dose doxorubicin elicits durable regressions of metastatic breast cancer. Cancer Research, 75(20), 4407–4415.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Yoo, B., Kavishwar, A., Wang, P., Ross, A., Pantazopoulos, P., Dudley, M., et al. (2017). Therapy targeted to the metastatic niche is effective in a model of stage IV breast cancer. Scientific Reports, 7, 45060.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Kim, J., Siverly, A. N., Chen, D., Wang, M., Yuan, Y., Wang, Y., et al. (2016). Ablation of miR-10b suppresses oncogene-induced mammary tumorigenesis and metastasis and reactivates tumor-suppressive pathways. Cancer Research, 76(21), 6424–6435.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Myers, C., Charboneau, A., Cheung, I., Hanks, D., & Boudreau, N. (2002). Sustained expression of homeobox D10 inhibits angiogenesis. The American Journal of Pathology, 161(6), 2099–2109.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Chai, G., Liu, N., Ma, J., Li, H., Oblinger, J. L., Prahalad, A. K., et al. (2010). MicroRNA-10b regulates tumorigenesis in neurofibromatosis type 1. Cancer Science, 101(9), 1997–2004.PubMedCrossRefGoogle Scholar
  51. 51.
    Tian, Y., Luo, A., Cai, Y., Su, Q., Ding, F., Chen, H., et al. (2010). MicroRNA-10b promotes migration and invasion through KLF4 in human esophageal cancer cell lines. The Journal of Biological Chemistry, 285(11), 7986–7994.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Ma, L., Young, J., Prabhala, H., Pan, E., Mestdagh, P., Muth, D., et al. (2010). MiR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nature Cell Biology, 12(3), 247–256.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Chen, D., Sun, Y., Wei, Y., Zhang, P., Rezaeian, A. H., Teruya-Feldstein, J., et al. (2012). LIFR is a breast cancer metastasis suppressor upstream of the Hippo-YAP pathway and a prognostic marker. Nature Medicine, 18(10), 1511–1517.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Johnson, R. W., Finger, E. C., Olcina, M. M., Vilalta, M., Aguilera, T., Miao, Y., et al. (2016). Induction of LIFR confers a dormancy phenotype in breast cancer cells disseminated to the bone marrow. Nature Cell Biology, 18(10), 1078–1089.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Luo, Q., Wang, C., Jin, G., Gu, D., Wang, N., Song, J., et al. (2015). LIFR functions as a metastasis suppressor in hepatocellular carcinoma by negatively regulating phosphoinositide 3-kinase/AKT pathway. Carcinogenesis, 36(10), 1201–1212.PubMedCrossRefGoogle Scholar
  56. 56.
    Sachdeva, M., Mito, J. K., Lee, C. L., Zhang, M., Li, Z., Dodd, R. D., et al. (2014). MicroRNA-182 drives metastasis of primary sarcomas by targeting multiple genes. The Journal of Clinical Investigation, 124(10), 4305–4319.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Segura, M. F., Hanniford, D., Menendez, S., Reavie, L., Zou, X., Alvarez-Diaz, S., et al. (2009). Aberrant miR-182 expression promotes melanoma metastasis by repressing FOXO3 and microphthalmia-associated transcription factor. Proceedings of the National Academy of Sciences of the United States of America, 106(6), 1814–1819.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Tavazoie, S. F., Alarcon, C., Oskarsson, T., Padua, D., Wang, Q., Bos, P. D., et al. (2008). Endogenous human microRNAs that suppress breast cancer metastasis. Nature, 451(7175), 147–152.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Song, G., Zhang, Y., & Wang, L. (2009). MicroRNA-206 targets notch3, activates apoptosis, and inhibits tumor cell migration and focus formation. The Journal of Biological Chemistry, 284(46), 31921–31927.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Png, K. J., Halberg, N., Yoshida, M., & Tavazoie, S. F. (2011). A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. Nature, 481(7380), 190–194.PubMedCrossRefGoogle Scholar
  61. 61.
    Zhang, Y., Yang, P., Sun, T., Li, D., Xu, X., Rui, Y., et al. (2013). MiR-126 and miR-126* repress recruitment of mesenchymal stem cells and inflammatory monocytes to inhibit breast cancer metastasis. Nature Cell Biology, 15(3), 284–294.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Liu, H., Patel, M. R., Prescher, J. A., Patsialou, A., Qian, D., Lin, J., et al. (2010). Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models. Proceedings of the National Academy of Sciences of the United States of America, 107(42), 18115–18120.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Malanchi, I., Santamaria-Martinez, A., Susanto, E., Peng, H., Lehr, H. A., Delaloye, J. F., et al. (2011). Interactions between cancer stem cells and their niche govern metastatic colonization. Nature, 481(7379), 85–89.PubMedCrossRefGoogle Scholar
  64. 64.
    Al-Hajj, M., Wicha, M. S., Benito-Hernandez, A., Morrison, S. J., & Clarke, M. F. (2003). Prospective identification of tumorigenic breast cancer cells. Proceedings of the National Academy of Sciences of the United States of America, 100(7), 3983–3988.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Yu, F., Yao, H., Zhu, P., Zhang, X., Pan, Q., Gong, C., et al. (2007). Let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell, 131(6), 1109–1123.PubMedCrossRefGoogle Scholar
  66. 66.
    Dangi-Garimella, S., Yun, J., Eves, E. M., Newman, M., Erkeland, S. J., Hammond, S. M., et al. (2009). Raf kinase inhibitory protein suppresses a metastasis signalling cascade involving LIN28 and let-7. The EMBO Journal, 28(4), 347–358.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Yun, J., Frankenberger, C. A., Kuo, W. L., Boelens, M. C., Eves, E. M., Cheng, N., et al. (2011). Signalling pathway for RKIP and Let-7 regulates and predicts metastatic breast cancer. The EMBO Journal, 30(21), 4500–4514.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Liu, C., Kelnar, K., Liu, B., Chen, X., Calhoun-Davis, T., Li, H., et al. (2011). The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nature Medicine, 17(2), 211–215.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Liu, C., Liu, R., Zhang, D., Deng, Q., Liu, B., Chao, H. P., et al. (2017). MicroRNA-141 suppresses prostate cancer stem cells and metastasis by targeting a cohort of pro-metastasis genes. Nature Communications, 8, 14270.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Tsai, J. H., Donaher, J. L., Murphy, D. A., Chau, S., & Yang, J. (2012). Spatiotemporal regulation of epithelial-mesenchymal transition is essential for squamous cell carcinoma metastasis. Cancer Cell, 22(6), 725–736.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Tsai, J. H., & Yang, J. (2013). Epithelial-mesenchymal plasticity in carcinoma metastasis. Genes & Development, 27(20), 2192–2206.CrossRefGoogle Scholar
  72. 72.
    Gregory, P. A., Bert, A. G., Paterson, E. L., Barry, S. C., Tsykin, A., Farshid, G., et al. (2008). The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nature Cell Biology, 10(5), 593–601.PubMedCrossRefGoogle Scholar
  73. 73.
    Park, S. M., Gaur, A. B., Lengyel, E., & Peter, M. E. (2008). The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes & Development, 22(7), 894–907.CrossRefGoogle Scholar
  74. 74.
    Burk, U., Schubert, J., Wellner, U., Schmalhofer, O., Vincan, E., Spaderna, S., et al. (2008). A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Reports, 9(6), 582–589.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Gregory, P. A., Bracken, C. P., Smith, E., Bert, A. G., Wright, J. A., Roslan, S., et al. (2011). An autocrine TGF-beta/ZEB/miR-200 signaling network regulates establishment and maintenance of epithelial-mesenchymal transition. Molecular Biology of the Cell, 22(10), 1686–1698.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Zhang, P., Wang, L., Rodriguez-Aguayo, C., Yuan, Y., Debeb, B. G., Chen, D., et al. (2014). MiR-205 acts as a tumour radiosensitizer by targeting ZEB1 and Ubc13. Nature Communications, 5, 5671.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Gibbons, D. L., Lin, W., Creighton, C. J., Rizvi, Z. H., Gregory, P. A., Goodall, G. J., et al. (2009). Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression. Genes & Development, 23(18), 2140–2151.CrossRefGoogle Scholar
  78. 78.
    Dykxhoorn, D. M., Wu, Y., Xie, H., Yu, F., Lal, A., Petrocca, F., et al. (2009). MiR-200 enhances mouse breast cancer cell colonization to form distant metastases. PLoS One, 4(9), e7181.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Korpal, M., Ell, B. J., Buffa, F. M., Ibrahim, T., Blanco, M. A., Celia-Terrassa, T., et al. (2011). Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nature Medicine, 17(9), 1101–1108.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Chou, J., Lin, J. H., Brenot, A., Kim, J. W., Provot, S., & Werb, Z. (2013). GATA3 suppresses metastasis and modulates the tumour microenvironment by regulating microRNA-29b expression. Nature Cell Biology, 15(2), 201–213.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Martello, G., Rosato, A., Ferrari, F., Manfrin, A., Cordenonsi, M., Dupont, S., et al. (2010). A microRNA targeting dicer for metastasis control. Cell, 141(7), 1195–1207.PubMedCrossRefGoogle Scholar
  82. 82.
    Chen, D., Sun, Y., Yuan, Y., Han, Z., Zhang, P., Zhang, J., et al. (2014). MiR-100 induces epithelial-mesenchymal transition but suppresses tumorigenesis, migration and invasion. PLoS Genetics, 10(2), e1004177.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Song, S. J., Poliseno, L., Song, M. S., Ala, U., Webster, K., Ng, C., et al. (2013). MicroRNA-antagonism regulates breast cancer stemness and metastasis via TET-family-dependent chromatin remodeling. Cell, 154(2), 311–324.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Krzeszinski, J. Y., Wei, W., Huynh, H., Jin, Z., Wang, X., Chang, T. C., et al. (2014). MiR-34a blocks osteoporosis and bone metastasis by inhibiting osteoclastogenesis and Tgif2. Nature, 512(7515), 431–435.PubMedCrossRefGoogle Scholar
  85. 85.
    Ell, B., Mercatali, L., Ibrahim, T., Campbell, N., Schwarzenbach, H., Pantel, K., et al. (2013). Tumor-induced osteoclast miRNA changes as regulators and biomarkers of osteolytic bone metastasis. Cancer Cell, 24(4), 542–556.PubMedCrossRefGoogle Scholar
  86. 86.
    Singh, R., Pochampally, R., Watabe, K., Lu, Z., & Mo, Y. Y. (2014). Exosome-mediated transfer of miR-10b promotes cell invasion in breast cancer. Molecular Cancer, 13, 256.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Zhuang, G., Wu, X., Jiang, Z., Kasman, I., Yao, J., Guan, Y., et al. (2012). Tumour-secreted miR-9 promotes endothelial cell migration and angiogenesis by activating the JAK-STAT pathway. The EMBO Journal, 31(17), 3513–3523.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Zhou, W., Fong, M. Y., Min, Y., Somlo, G., Liu, L., Palomares, M. R., et al. (2014). Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell, 25(4), 501–515.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Fong, M. Y., Zhou, W., Liu, L., Alontaga, A. Y., Chandra, M., Ashby, J., et al. (2015). Breast-cancer-secreted miR-122 reprograms glucose metabolism in premetastatic niche to promote metastasis. Nature Cell Biology, 17(2), 183–194.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Zhang, L., Zhang, S., Yao, J., Lowery, F. J., Zhang, Q., Huang, W. C., et al. (2015). Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth. Nature, 527(7576), 100–104.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Merritt, W. M., Lin, Y. G., Han, L. Y., Kamat, A. A., Spannuth, W. A., Schmandt, R., et al. (2008). Dicer, Drosha, and outcomes in patients with ovarian cancer. The New England Journal of Medicine, 359(25), 2641–2650.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Torres, A., Torres, K., Paszkowski, T., Jodlowska-Jedrych, B., Radomanski, T., Ksiazek, A., et al. (2011). Major regulators of microRNAs biogenesis Dicer and Drosha are down-regulated in endometrial cancer. Tumour Biology, 32(4), 769–776.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Rupaimoole, R., Ivan, C., Yang, D., Gharpure, K. M., Wu, S. Y., Pecot, C. V., et al. (2016). Hypoxia-upregulated microRNA-630 targets Dicer, leading to increased tumor progression. Oncogene, 35(33), 4312–4320.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Su, X., Chakravarti, D., Cho, M. S., Liu, L., Gi, Y. J., Lin, Y. L., et al. (2010). TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs. Nature, 467(7318), 986–990.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    van den Beucken, T., Koch, E., Chu, K., Rupaimoole, R., Prickaerts, P., Adriaens, M., et al. (2014). Hypoxia promotes stem cell phenotypes and poor prognosis through epigenetic regulation of DICER. Nature Communications, 5, 5203.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Shen, J., Xia, W., Khotskaya, Y. B., Huo, L., Nakanishi, K., Lim, S. O., et al. (2013). EGFR modulates microRNA maturation in response to hypoxia through phosphorylation of AGO2. Nature, 497(7449), 383–387.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Salmena, L., Poliseno, L., Tay, Y., Kats, L., & Pandolfi, P. P. (2011). A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell, 146(3), 353–358.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Bosson, A. D., Zamudio, J. R., & Sharp, P. A. (2014). Endogenous miRNA and target concentrations determine susceptibility to potential ceRNA competition. Molecular Cell, 56(3), 347–359.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Denzler, R., Agarwal, V., Stefano, J., Bartel, D. P., & Stoffel, M. (2014). Assessing the ceRNA hypothesis with quantitative measurements of miRNA and target abundance. Molecular Cell, 54(5), 766–776.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Poliseno, L., Salmena, L., Zhang, J., Carver, B., Haveman, W. J., & Pandolfi, P. P. (2010). A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature, 465(7301), 1033–1038.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Karreth, F. A., Tay, Y., Perna, D., Ala, U., Tan, S. M., Rust, A. G., et al. (2011). In vivo identification of tumor-suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma. Cell, 147(2), 382–395.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Tay, Y., Kats, L., Salmena, L., Weiss, D., Tan, S. M., Ala, U., et al. (2011). Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs. Cell, 147(2), 344–357.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Department of Experimental Radiation OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.UTHealth Graduate School of Biomedical SciencesThe University of Texas MD Anderson Cancer CenterHoustonUSA
  3. 3.Department of Molecular and Cellular OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA

Personalised recommendations