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miR clusters target cellular functional complexes by defining their degree of regulatory freedom

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Abstract

Using the two paralog miR-23∼27∼24 clusters as an example and combining experimental and clinical data in a systematical approach to microRNA (miR) function and dysregulation, a complex picture of their roles in cancer is drawn. Various findings appear to be contradictory to a larger extent and cannot be fully explained by the classical regulatory network models and feedback loops that are mainly considered by one-to-one regulatory interactions of the involved molecules. Here, we propose an extended model of the regulatory role of miRs that, at least, supplements the usually considered single/oligo-target regulation of certain miRs. The cellular availability of the participating miR members in this model reflects an upper hierarchy level of intracellular and extracellular environmental influences, such as neighboring cells, soluble factors, hypoxia, chemotherapeutic drugs, and irradiation, among others. The novel model is based on the understanding of cellular functional complexes, such as for apoptosis, migration, and proliferation. These complexes consist of many regulatory components that can be targeted by miR cluster members to a different extent but may affect the functional complex in different ways. We propose that the final miR-related effect is a result of the possible degree of regulatory freedom provided by the miR effects on the whole functional complex structure. This degree of regulatory freedom defines to which extent the cellular functional complex can react in response to regulatory triggers, also understood as sensitization (more regulatory response options) or de-sensitization (less regulatory response options) of the system rather than single molecules.

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References

  1. Lindner, K., Haier, J., Wang, Z., Watson, D. I., Hussey, D. J., & Hummel, R. (2015). Circulating microRNAs: emerging biomarkers for diagnosis and prognosis in patients with gastrointestinal cancers. Clinical Science (London), 128(1), 1–15.

    Article  CAS  Google Scholar 

  2. Hummel, R., Maurer, J., & Haier, J. (2011). MicroRNAs in brain tumors: a new diagnostic and therapeutic perspective? Molecular Neurobiology, 44(3), 223–234.

    Article  CAS  PubMed  Google Scholar 

  3. Lopez-Camarillo, C., Marchat, L. A., Arechaga-Ocampo, E., Perez-Plasencia, C., Del Moral-Hernandez, O., Castaneda-Ortiz, E. J., et al. (2012). MetastamiRs: non-coding microRNAs driving cancer invasion and metastasis. International Journal of Molecular Sciences, 13(2), 1347–1379.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Calin, G. A., Sevignani, C., Dan Dumitru, C., Hyslop, T., Noch, E., Yendamuri, S., et al. (2004). Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proceedings of the National Academy of Sciences of the United States of America, 101, 2999–3004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Lal, A., Kim, H. H., Abdelmohsen, K., Kuwano, Y., Pullmann, R., Jr., Srikantan, S., et al. (2008). P16(INK4a) translation suppressed by miR-24. PLoS One, 3(3), e1864.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Garzon, R., Fabbri, M., Cimmino, A., Calin, G. A., & Croce, C. M. (2006). MicroRNA expression and function in cancer. Trends in Molecular Medicine, 12(12), 580–587.

    Article  CAS  PubMed  Google Scholar 

  7. Lynam-Lennon, N., Maher, S. G., & Reynolds, J. V. (2009). The roles of microRNA in cancer and apoptosis. Biological Reviews of the Cambridge Philosophical Society, 84(1), 55–71.

    Article  PubMed  Google Scholar 

  8. Grimson, A., Farh, K. K., Johnston, W. K., Garrett-Engele, P., Lim, L. P., & Bartel, D. P. (2007). MiR targeting specificity in mammals: determinants beyond seed pairing. Molecular Cell, 27(1), 91–105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Huang, J. C., Babak, T., Corson, T. W., Chua, G., Khan, S., Gallie, B. L., et al. (2007). Using expression profiling data to identify human microRNA targets. Nature Methods, 4(12), 1045–1049.

    Article  CAS  PubMed  Google Scholar 

  10. Hurst, D. R., Edmonds, M. D., & Welch, D. R. (2009). Metastamir: the field of metastasis-regulatory microRNA is spreading. Cancer Research, 69, 7495–7749.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Gomes, C. C., & Gomez, R. S. (2008). MicroRNA and oral cancer: future perspectives. Oral Oncology, 44(10), 910–914.

    Article  CAS  PubMed  Google Scholar 

  12. Griffiths-Jones, S., Saini, H. K., van Dongen, S., & Enright, A. J. (2008). miRBase: tools for miR genomics. Nucleic Acids Research, 36, D154–D158.

    Article  CAS  PubMed  Google Scholar 

  13. Altuvia, Y., Landgraf, P., Lithwick, G., Elefant, N., Pfeffer, S., Aravin, A., et al. (2005). Clustering and conservation patterns of human microRNAs. Nucleic Acids Research, 33, 2697–2706.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Yu, J., Wang, F., Yang, G. H., Wang, F. L., Ma, Y. N., Du, Z. W., et al. (2006). Human microRNA clusters: genomic organization and expression profile in leukemia cell lines. Biochemical and Biophysical Research Communications, 349, 59–68.

    Article  CAS  PubMed  Google Scholar 

  15. An, J., Pan, Y., Yan, Z., Li, W., Cui, J., Yuan, J., et al. (2013). MiR-23a in amplified 19p13.13 loci targets metallothionein 2A and promotes growth in gastric cancer cells. Journal of Cellular Biochemistry, 114(9), 2160–2169.

    Article  CAS  PubMed  Google Scholar 

  16. Stark, M. S., Tyagi, S., Nancarrow, D. J., Boyle, G. M., Cook, A. L., Whiteman, D. C., et al. (2010). Characterization of the melanoma miRNAome by deep sequencing. PLoS One, 5(3), e9685.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Chhabra, R., Dubey, R., & Saini, N. (2010). Cooperative and individualistic functions of the microRNAs in the miR-23a∼27a∼24-2 cluster and its implication in human diseases. Molecular Cancer, 9, 232.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Lujambio, A., Calin, G. A., Villanueva, A., Ropero, S., Sánchez-Céspedes, M., Blanco, D., et al. (2008). A microRNA DNA methylation signature for human cancer metastasis. Proceedings of the National Academy of Sciences of the United States of America, 105(36), 13556–13561.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Quintavalle, C., Mangani, D., Roscigno, G., Romano, G., Diaz-Lagares, A., Iaboni, M., et al. (2013). MiR-221/222 target the DNA methyltransferase MGMT in glioma cells. PLoS One, 8(9), e74466.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Saini, H. K., Griffiths-Jones, S., & Enright, A. J. (2007). Genomic analysis of human microRNA transcripts. Proceedings of the National Academy of Sciences of the United States of America, 104, 17719–17724.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Sandoval, J., Díaz-Lagares, A., Salgado, R., Servitje, O., Climent, F., Ortiz-Romero, P. L., et al. (2015). MicroRNA expression profiling and DNA methylation signature for deregulated microRNA in cutaneous T-cell lymphoma. Journal of Investigative Dermatology, 135(4), 1128–1137.

    Article  CAS  PubMed  Google Scholar 

  22. He, X. X., Kuang, S. Z., Liao, J. Z., Xu, C. R., Chang, Y., Wu, Y. L., et al. (2015). The regulation of microRNA expression by DNA methylation in hepatocellular carcinoma. Molecular Biosystems, 11(2), 532–539.

    Article  CAS  PubMed  Google Scholar 

  23. He, Y., Meng, C., Shao, Z., Wang, H., & Yang, S. (2014). MiR-23a functions as a tumor suppressor in osteosarcoma. Cellular Physiology and Biochemistry, 34, 1485–1496.

    Article  CAS  PubMed  Google Scholar 

  24. Xishan, Z., Xianjun, L., Ziying, L., Guangxin, C., & Gang, L. (2014). The malignancy suppression role of miR-23a by targeting the BCR/ABL oncogene in chromic myeloid leukemia. Cancer Gene Therapy, 21(9), 397–404.

    Article  CAS  PubMed  Google Scholar 

  25. Wang, S., Zhang, R., Claret, F. X., & Yang, H. (2014). Involvement of microRNA-24 and DNA methylation in resistance of nasopharyngeal carcinoma to ionizing radiation. Molecular Cancer Therapeutics, 13(12), 3163–3174.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Geng, J., Luo, H., Pu, Y., Zhou, Z., Wu, X., Xu, W., et al. (2012). Methylation mediated silencing of miR-23b expression and its role in glioma stem cells. Neuroscience Letters, 528(2), 185–189.

    Article  CAS  PubMed  Google Scholar 

  27. Majid, S., Dar, A. A., Saini, S., Arora, S., Shahryari, V., Zaman, M. S., et al. (2012). miR-23b represses proto-oncogene SRC kinase and functions as methylation-silenced tumor suppressor with diagnostic and prognostic significance in prostate cancer. Cancer Research, 72(24), 6435–6446.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Cheng, Y. Y., Kirschner, M. B., Cheng, N. C., Gattani, S., Klebe, S., Edelman, J. J., et al. (2013). ZIC1 is silenced and has tumor suppressor function in malignant pleural mesothelioma. Journal of Thoracic Oncology, 8(10), 1317–1328.

    Article  CAS  PubMed  Google Scholar 

  29. Li, X., Liu, X., Xu, W., Zhou, P., Gao, P., Jiang, S., et al. (2013). c-MYC-regulated miR-23a/24-2/27a cluster promotes mammary carcinoma cell invasion and hepatic metastasis by targeting Sprouty2. Journal of Biological Chemistry, 288(25), 18121–18133.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Scheibner, K. A., Teaboldt, B., Hauer, M. C., Chen, X., Cherukuri, S., Guo, Y., et al. (2012). MiR-27a functions as a tumor suppressor in acute leukemia by regulating 14-3-3θ. PLoS One, 7(12), e50895.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Zheng, H., Li, W., Wang, Y., Xie, T., Cai, Y., Wang, Z., et al. (2014). miR-23a inhibits E-cadherin expression and is regulated by AP-1 and NFAT4 complex during Fas-induced EMT in gastrointestinal cancer. Carcinogenesis, 35(1), 173–183.

    Article  CAS  PubMed  Google Scholar 

  32. Lin, H., Qian, J., Castillo, A. C., Long, B., Keyes, K. T., Chen, G., et al. (2011). Effect of miR-23 on oxidant-induced injury in human retinal pigment epithelial cells. Investigative Ophthalmology & Visual Science, 52(9), 6308–6314.

    Article  CAS  Google Scholar 

  33. Lin, Z., Murtaza, I., Wang, K., Jiao, J., Gao, J., & Li, P. F. (2009). miR-23a functions downstream of NFATc3 to regulate cardiac hypertrophy. Proceedings of the National Academy of Sciences of the United States of America, 106, 12103–12108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Saumet, A., Vetter, G., Bouttier, M., Portales-Casamar, E., Wasserman, W. W., Maurin, T., et al. (2009). Transcriptional repression of microRNA genes by PML-RARA increases expression of key cancer proteins in acute promyelocytic leukemia. Blood, 113, 412–421.

    Article  CAS  PubMed  Google Scholar 

  35. Wang, N., Zhu, M., Tsao, S. W., Man, K., Zhang, Z., & Feng, Y. (2013). MiR-23a-mediated inhibition of topoisomerase 1 expression potentiates cell response to etoposide in human hepatocellular carcinoma. Molecular Cancer, 12(1), 119.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Zaidi, S. K., Dowdy, C. R., van Wijnen, A. J., Lian, J. B., Raza, A., Stein, J. L., et al. (2009). Altered Runx1 subnuclear targeting enhances myeloid cell proliferation and blocks differentiation by activating a miR-24/MKP-7/MAP kinase network. Cancer Research, 69(21), 8249–8255.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hassan, M. Q., Gordon, J. A., Beloti, M. M., Croce, C. M., van Wijnen, A. J., Stein, J. L., et al. (2010). A network connecting Runx2, SATB2, and the miR-23a∼27a∼24-2 cluster regulates the osteoblast differentiation program. Proceedings of the National Academy of Sciences of the United States of America, 107(46), 19879–19884.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Huang, S., He, X., Ding, J., Liang, L., Zhao, Y., Zhang, Z., et al. (2008). Upregulation of miR-23a∼27a∼24 decreases transforming growth factor-beta-induced tumor-suppressive activities in human hepatocellular carcinoma cells. International Journal of Cancer, 123(4), 972–978.

    Article  CAS  PubMed  Google Scholar 

  39. Wang, B., Hsu, S. H., Frankel, W., Ghoshal, K., & Jacob, S. T. (2012). Stat3-mediated activation of microRNA-23a suppresses gluconeogenesis in hepatocellular carcinoma by down-regulating glucose-6-phosphatase and peroxisome proliferator-activated receptor gamma, coactivator 1 alpha. Hepatology, 56(1), 186–197.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Cao, M., Seike, M., Soeno, C., Mizutani, H., Kitamura, K., Minegishi, Y., et al. (2012). MiR-23a regulates TGF-β-induced epithelial-mesenchymal transition by targeting E-cadherin in lung cancer cells. International Journal of Oncology, 41(3), 869–875.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. McKenna, D. J., Patel, D., & McCance, D. J. (2014). miR-24 and miR-205 expression is dependent on HPV onco-protein expression in keratinocytes. Virology, 448, 210–216.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Donadelli, M., Dando, I., Fiorini, C., & Palmieri, M. (2014). Regulation of miR-23b expression and its dual role on ROS production and tumor development. Cancer Letters, 349, 107–113.

    Article  CAS  PubMed  Google Scholar 

  43. Chintharlapalli, S., Papineni, S., Abdelrahim, M., Abudayyeh, A., Jutooru, I., Chadalapaka, G., et al. (2009). Oncogenic miR-27a is a target for anticancer agent methyl 2-cyano-3,11-dioxo-18beta-olean-1,12-dien-30-oate in colon cancer cells. International Journal of Cancer, 125(8), 1965–1974.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Hermeking, H. (2009). p53 enters the microRNA world. Cancer Cell, 12, 414–418.

    Article  CAS  Google Scholar 

  45. Suzuki, H. I., Yamagata, K., Sugimoto, K., Iwamoto, T., Kato, S., & Miyazono, K. (2009). Modulation of microRNA processing by p53. Nature, 460, 529–533.

    Article  CAS  PubMed  Google Scholar 

  46. Wang, N., Zhua, M., Wang, X., Tan, H. Y., Tsao, S. W., & Feng, Y. (2014). Berberine-induced tumor suppressor p53 up-regulation gets involved in the regulatory network of MIR-23a in hepatocellular carcinoma. Biochimica et Biophysica Acta, 1839, 849–857.

    Article  CAS  PubMed  Google Scholar 

  47. Yang, R., Schlehe, B., Hemminki, K., Sutter, C., Bugert, P., Wappenschmidt, B., et al. (2010). A genetic variant in the pre-miR-27a oncogene is associated with a reduced familial breast cancer risk. Breast Cancer Research and Treatment, 121(3), 693–702.

    Article  PubMed  Google Scholar 

  48. Xi, Y., Shalgi, R., Fodstad, O., Pilpel, Y., & Ju, J. (2006). Differentially regulated micro-RNAs and actively translated messenger RNA transcripts by tumor suppressor p53 in colon cancer. Clinical Cancer Research, 12(7 Pt 1), 2014–2024.

    Article  CAS  PubMed  Google Scholar 

  49. Arisawa, T., Tahara, T., Shibata, T., Nagasaka, M., Nakamura, M., Kamiya, Y., et al. (2007). A polymorphism of microRNA 27a genome region is associated with the development of gastric mucosal atrophy in Japanese male subjects. Digestive Diseases and Sciences, 52(7), 1691–1697.

    Article  CAS  PubMed  Google Scholar 

  50. Luzi, E., Marini, F., Giusti, F., Galli, G., Cavalli, L., & Brandi, M. L. (2012). The negative feedback-loop between the oncomir Mir-24-1 and menin modulates the Men1 tumorigenesis by mimicking the “Knudson’s second hit”. PLoS One, 7(6), e39767.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Tanaka, K., Miyata, H., Sugimura, K., Fukuda, S., Kanemura, T., Yamashita, K., et al. (2015). miR-27 is associated with chemoresistance in esophageal cancer through transformation of normal fibroblasts to cancer-associated fibroblasts. Carcinogenesis, 36(8), 894–903.

    Article  PubMed  Google Scholar 

  52. Cai, Z. G., Zhang, S. M., Zhang, H., Zhou, Y. Y., Wu, H. B., & Xu, X. P. (2013). Aberrant expression of microRNAs involved in epithelial-mesenchymal transition of HT-29 cell line. Cell Biology International, 37(7), 669–674.

    Article  CAS  PubMed  Google Scholar 

  53. Chan, M. C., Hilyard, A. C., Wu, C., Davis, B. N., Hill, N. S., Lal, A., et al. (2010). Molecular basis for antagonism between PDGF and the TGFbeta family of signalling pathways by control of miR-24 expression. EMBO Journal, 29(3), 559–573.

    Article  CAS  PubMed  Google Scholar 

  54. Chhabra, R., Adlakha, Y. K., Hariharan, M., Scaria, V., & Saini, N. (2009). Upregulation of miR-23a-27a-24-2 cluster induces caspase-dependent and -independent apoptosis in human embryonic kidney cells. PLoS One, 4(6), e5848.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Yu, S., Cao, H., Shen, B., & Feng, J. (2015). Tumor-derived exosomes in cancer progression and treatment failure. Oncotarget, 6(35), 37151–68. doi:10.18632/oncotarget.6022.

    PubMed  PubMed Central  Google Scholar 

  56. Chhabra, R., Dubey, R., & Saini, N. (2011). Gene expression profiling indicate role of ER stress in miR-23a∼27a∼24-2 cluster induced apoptosis in HEK293T cells. RNA Biology, 8(4), 648–664.

    Article  CAS  PubMed  Google Scholar 

  57. Roy, L., Bikorimana, E., Lapid, D., Choi, H., Nguyen, T., & Dahl, R. (2015). MiR-24 is required for hematopoietic differentiation of mouse embryonic stem cells. PLoS Genetics, 11(1), e1004959.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Kong, K. Y., Owens, K. S., Rogers, J. H., Mullenix, J., Velu, C. S., Grimes, H. L., et al. (2010). MIR-23A microRNA cluster inhibits B-cell development. Experimental Hematology, 38(8), 629.e1–640.e1.

    Article  CAS  Google Scholar 

  59. Ruan, W., Xu, J. M., Li, S. B., Yuan, L. Q., & Dai, R. P. (2012). Effects of down-regulation of miR-23a on TNF-a-induced endothelial cell apoptosis through caspase-dependent pathways. Cardiovascular Research, 93, 623–632.

    Article  CAS  PubMed  Google Scholar 

  60. Mao, J., Lv, Z., & Zhuang, Y. (2014). MicroRNA-23a is involved in tumor necrosis factor-α induced apoptosis in mesenchymal stem cells and myocardial infarction. Experimental and Molecular Pathology, 97(1), 23–30.

    Article  CAS  PubMed  Google Scholar 

  61. Chen, Q., Xu, J., Li, L., Li, H., Mao, S., Zhang, F., et al. (2014). MicroRNA-23a/b and microRNA-27a/b suppress Apaf-1 protein and alleviate hypoxia-induced neuronal apoptosis. Cell Death & Disease, 5, e1132.

    Article  CAS  Google Scholar 

  62. Siegel, C., Li, J., Liu, F., Benashski, S. E., & McCullough, L. D. (2011). miR-23a regulation of X-linked inhibitor of apoptosis (XIAP) contributes to sex differences in the response to cerebral ischemia. Proceedings of the National Academy of Sciences of the United States of America, 108(28), 11662–11667.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Veliceasa, D., Biyashev, D., Qin, G., Misener, S., Mackie, A. R., Kishore, R., & Volpert, O. V. (2015). Therapeutic manipulation of angiogenesis with miR-27b. Vascular Cell, 7, 6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Yang, X., Zhou, Y., Peng, S., Wu, L., Lin, H. Y., Wang, S., et al. (2012). Differentially expressed plasma microRNAs in premature ovarian failure patients and the potential regulatory function of mir-23a in granulosa cell apoptosis. Reproduction, 144(2), 235–244.

    Article  CAS  PubMed  Google Scholar 

  65. Bao, L., Zhao, J., Dai, X., Wang, Y., Ma, R., Su, Y., et al. (2014). Correlation between miR-23a and onset of hepatocellular carcinoma. Clinics and Research in Hepatology and Gastroenterology, 38(3), 318–330.

    Article  CAS  PubMed  Google Scholar 

  66. Shang, J., Yang, F., Wang, Y., Wang, Y., Xue, G., Mei, Q., et al. (2014). MicroRNA-23a antisense enhances 5-fluorouracil chemosensitivity through APAF-1/caspase-9 apoptotic pathway in colorectal cancer cells. Journal of Cellular Biochemistry, 115(4), 772–784.

    Article  CAS  PubMed  Google Scholar 

  67. Liu, N., Sun, Y. Y., Zhang, X. W., Chen, S., Wang, Y., Zhang, Z. X., et al. (2015). Oncogenic miR-23a in pancreatic ductal adenocarcinogenesis via inhibiting APAF1. Digestive Diseases and Sciences, 60, 2000–2008.

    Article  CAS  PubMed  Google Scholar 

  68. Yong, F. L., Wang, C. W., Roslani, A. C., & Law, C. W. (2014). The involvement of miR-23a/APAF1 regulation axis in colorectal cancer. International Journal of Molecular Sciences, 15(7), 11713–11729.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Zhang, X. W., Liu, N., Chen, S., Wang, Y. E., Sun, K. L., Xu, Z. M., et al. (2015). Upregulation of microRNA-23a regulates proliferation and apoptosis by targeting APAF-1 in laryngeal carcinoma. Oncology Letters, 10(1), 410–416.

    PubMed  PubMed Central  Google Scholar 

  70. Lian, S., Shi, R., Bai, T., Liu, Y., Miao, W., Wang, H., et al. (2013). Anti-miRNA-23a oligonucleotide suppresses glioma cells growth by targeting apoptotic protease activating factor-1. Current Pharmaceutical Design, 19(35), 6382–6389.

    Article  CAS  PubMed  Google Scholar 

  71. Gindin, Y., Jiang, Y., Francis, P., Walker, R. L., Abaan, O. D., Zhu, Y. J., et al. (2015). miR-23 impairs bone differentiation in osteosarcoma via down-regulation of GJA1. Frontiers in Genetics, 6, 233.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Cheng, L., Yang, T., Kuang, Y., Kong, B., Yu, S., Shu, H., et al. (2014). MicroRNA-23a promotes neuroblastoma cell metastasis by targeting CDH1. Oncology Letters, 3, 839–845.

    Google Scholar 

  73. Li, B., Sun, M., Gao, F., Liu, W., Yang, Y., Liu, H., et al. (2013). Up-regulated expression of miR-23a/b targeted the pro-apoptotic Fas in radiation-induced thymic lymphoma. Cellular Physiology and Biochemistry, 32, 1729–1740.

    Article  CAS  PubMed  Google Scholar 

  74. Loftus, J. C., Ross, J. T., Paquette, K. M., Paulino, V. M., Nasser, S., Yang, Z., et al. (2012). miRNA expression profiling in migrating glioblastoma cells, regulation of cell migration and invasion by miR-23b via targeting of PYK2. PLoS One, 7(6), e39818.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Leone, V., Langella, C., D’Angelo, D., Mussnich, P., Wierinckx, A., Terracciano, L., et al. (2014). Mir-23b and miR-130b expression is downregulated in pituitary adenomas. Molecular and Cellular Endocrinology, 390(1–2), 1–7.

    Article  CAS  PubMed  Google Scholar 

  76. Hu, X., Chen, D., Cui, Y., Li, Z., & Huang, J. (2013). Targeting microRNA-23a to inhibit glioma cell invasion via HOXD10. Scientific Reports, 3, 3423.

    PubMed  PubMed Central  Google Scholar 

  77. Cao, M., Li, Y., Lu, H., Meng, Q., Wang, L., Cai, L., et al. (2014). MiR-23a-mediated migration/invasion is rescued by its target, IRS-1, in non-small cell lung cancer cells. Journal of Cancer Research and Clinical Oncology, 140(10), 1661–1670.

    Article  CAS  PubMed  Google Scholar 

  78. Liu, X., Ru, J., Zhang, J., Zhu, L. H., Liu, M., Li, X., & Tang, H. (2013). miR-23a targets interferon regulatory factor 1 and modulates cellular proliferation and paclitaxel-induced apoptosis in gastric adenocarcinoma cells. PLoS One, 8, e64707.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Zhu, L. H., Liu, T., Tang, H., Tian, R. Q., Su, C., Liu, M., et al. (2010). MiR-23a promotes the growth of gastric adenocarcinoma cell line MGC803 and downregulates interleukin-6 receptor. FEBS Journal, 277(18), 3726–3734.

    Article  CAS  PubMed  Google Scholar 

  80. Aghaee-Bakhtiari, S. H., Arefian, E., Naderi, M., Noorbakhsh, F., Nodouzi, V., Asgari, M., et al. (2015). MAPK and JAK/STAT pathways targeted by miR-23a and miR-23b in prostate cancer, computational and in vitro approaches. Tumor Biology, 36(6), 4203–4212.

    Article  CAS  PubMed  Google Scholar 

  81. Huang, T. T., Ping, Y. H., Wang, A. M., Ke, C. C., Fang, W. L., Huang, K. H., et al. (2015). The reciprocal regulation loop of Notch2 pathway and miR-23b in controlling gastric carcinogenesis. Oncotarget, 6(20), 18012–18026.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Cai, S., Chen, R., Li, X., Cai, Y., Ye, Z., Li, S., et al. (2015). Downregulation of microRNA-23a suppresses prostate cancer metastasis by targeting the PAK6-LIMK1 signaling pathway. Oncotarget, 6(6), 3904–3917.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Liu, X., Liu, Q., Fan, Y., Wang, S., Liu, X., Zhu, L., et al. (2014). Downregulation of PPP2R5E expression by miR-23a suppresses apoptosis to facilitate the growth of gastric cancer cells. FEBS Letters, 588(17), 3160–3169.

    Article  CAS  PubMed  Google Scholar 

  84. Ishteiwy, R. A., Ward, T. M., Dykxhoorn, D. M., & Burnstein, K. L. (2012). The miR-23b/-27b cluster suppresses the metastatic phenotype of castration-resistant prostate cancer cells. PLoS One, 7(12), e52106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Wang, G., Li, B., Fu, Y., He, M., Wang, J., Shen, P., et al. (2015). miR-23a suppresses proliferation of osteosarcoma cells by targeting SATB1. Tumor Biology, 36(6), 4715–4721.

    Article  CAS  PubMed  Google Scholar 

  86. Luo, Z., Feng, X., Wang, H., Xu, W., Zhao, Y., Ma, W., et al. (2015). Mir-23a induces telomere dysfunction and cellular senescence by inhibiting TRF2 expression. Aging Cell, 14, 391–399.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Chen, L., Han, L., Zhang, K., Shi, Z., Zhang, J., Zhang, A., et al. (2012). VHL regulates the effects of miR-23b on glioma survival and invasion via suppression of HIF-1α/VEGF and β-catenin/Tcf-4 signaling. Neuro-Oncology, 14(8), 1026–1036.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Majid, S., Dar, A. A., Saini, S., Deng, G., Chang, I., Greene, K., et al. (2013). MicroRNA-23b functions as a tumor suppressor by regulating ZEB1 in bladder cancer. PLoS One, 8(7), e67686.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Xu, L., Chen, Z., Xue, F., Chen, W., Ma, R., Cheng, S., et al. (2015). MicroRNA-24 inhibits growth, induces apoptosis, and reverses radioresistance in laryngeal squamous cell carcinoma by targeting X-linked inhibitor of apoptosis protein. Cancer Cell International, 15, 61.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Lal, A., Navarro, F., Maher, C. A., Maliszewski, L. E., Yan, N., O’Day, E., et al. (2009). miR-24 inhibits cell proliferation by targeting E2F2, MYC, and other cell-cycle genes via binding to “seedless” 3′UTR microRNA recognition elements. Molecular Cell, 35(5), 610–625.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Liu, X., Wang, A., Heidbreder, C. E., Jiang, L., Yu, J., Kolokythas, A., et al. (2010). MicroRNA-24 targeting RNA-binding protein DND1 in tongue squamous cell carcinoma. FEBS Letters, 584(18), 4115–4120.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Mishra, P. J., Song, B., Mishra, P. J., Wang, Y., Humeniuk, R., Banerjee, D., et al. (2009). MiR-24 tumor suppressor activity is regulated independent of p53 and through a target site polymorphism. PLoS One, 4(12), e8445.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Mishra, P. J., Humeniuk, R., Mishra, P. J., Longo-Sorbello, G. S., Banerjee, D., & Bertino, J. R. (2007). A miR-24 microRNA binding-site polymorphism in dihydrofolate reductase gene leads to methotrexate resistance. Proceedings of the National Academy of Sciences of the United States of America, 104(33), 13513–13518.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Qin, W., Shi, Y., Zhao, B., Yao, C., Jin, L., Ma, J., et al. (2010). miR-24 regulates apoptosis by targeting the open reading frame (ORF) region of FAF1 in cancer cells. PLoS One, 5(2), e9429.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Inoguchi, S., Seki, N., Chiyomaru, T., Ishihara, T., Matsushita, R., Mataki, H., et al. (2014). Tumor-suppressive miR-24-1 inhibits cancer cell proliferation through targeting FOXM1 in bladder cancer. FEBS Letters, 588(17), 3170–3179.

    Article  CAS  PubMed  Google Scholar 

  96. Srivastava, N., Manvati, S., Srivastava, A., Pal, R., Kalaiarasan, P., Chattopadhyay, S., et al. (2011). miR-24-2 controls H2AFX expression regardless of gene copy number alteration and induces apoptosis by targeting antiapoptotic gene BCL-2: a potential for therapeutic intervention. Breast Cancer Research, 13(2), R39. doi:10.1186/bcr2861.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Lal, A., Pan, Y., Navarro, F., Dykxhoorn, D. M., Moreau, L., Meire, E., et al. (2009). miR-24-mediated downregulation of H2AX suppresses DNA repair in terminally differentiated blood cells. Nature Structural & Molecular Biology, 16(5), 492–498.

    Article  CAS  Google Scholar 

  98. Song, L., Yang, J., Duan, P., Xu, J., Luo, X., Luo, F., et al. (2013). MicroRNA-24 inhibits osteosarcoma cell proliferation both in vitro and in vivo by targeting LPAAT β. Archives of Biochemistry and Biophysics, 535, 128–135.

    Article  CAS  PubMed  Google Scholar 

  99. Xu, W., Liu, M., Peng, X., Zhou, P., Zhou, J., Xu, K., et al. (2013). miR-24-3p and miR-27a-3p promote cell proliferation in glioma cells via cooperative regulation of MXI1. International Journal of Oncology, 42(2), 757–766.

    PubMed  Google Scholar 

  100. Zhao, G., Liu, L., Zhao, T., Jin, S., Jiang, S., Cao, S., et al. (2015). Upregulation of miR-24 promotes cell proliferation by targeting NAIF1 in non-small cell lung cancer. Tumor Biology, 36(5), 3693–3701.

    Article  CAS  PubMed  Google Scholar 

  101. To, K. H., Pajovic, S., Gallie, B. L., & Thériault, B. L. (2012). Regulation of p14ARF expression by miR-24, a potential mechanism compromising the p53 response during retinoblastoma development. BMC Cancer, 12, 69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Lin, S. C., Liu, C. J., Lin, J. A., Chiang, W. F., Hung, P. S., & Chang, K. W. (2010). miR-24 up-regulation in oral carcinoma, positive association from clinical and in vitro analysis. Oral Oncology, 46(3), 204–208.

    Article  CAS  PubMed  Google Scholar 

  103. Giglio, S., Cirombella, R., Amodeo, R., Portaro, L., Lavra, L., & Vecchione, A. (2013). MicroRNA miR-24 promotes cell proliferation by targeting the CDKs inhibitors p27Kip1 and p16INK4a. Journal of Cellular Physiology, 228(10), 2015–2023.

    Article  CAS  PubMed  Google Scholar 

  104. Martin, E. C., Elliott, S., Rhodes, L. V., Antoon, J. W., Fewell, C., Zhu, Y., Driver, J. L., et al. (2014). Preferential star strand biogenesis of pre-miR-24-2 targets PKC-alpha and suppresses cell survival in MCF-7 breast cancer cells. Molecular Carcinogenesis, 53(1), 38–48.

    Article  CAS  PubMed  Google Scholar 

  105. Duan, Y., Hu, L., Liu, B., Yu, B., Li, J., Yan, M., et al. (2014). Tumor suppressor miR-24 restrains gastric cancer progression by downregulating RegIV. Molecular Cancer, 13, 127.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Papadimitriou, E., Vasilaki, E., Vorvis, C., Iliopoulos, D., Moustakas, A., Kardassis, D., et al. (2012). Differential regulation of the two RhoA-specific GEF isoforms NET1/NET1A by TGF-β and miR-24, role in epithelial-to-mesenchymal transition. Oncogene, 31(23), 2862–2875.

    Article  CAS  PubMed  Google Scholar 

  107. Guo, Y., Fu, W., Chen, H., Shang, C., & Zhong, M. (2012). miR-24 functions as a tumor suppressor in Hep2 laryngeal carcinoma cells partly through down-regulation of the S100A8 protein. Oncology Reports, 27(4), 1097–1103.

    CAS  PubMed  Google Scholar 

  108. Ma, Y., She, X. G., Ming, Y. Z., & Wan, Q. Q. (2014). miR-24 promotes the proliferation and invasion of HCC cells by targeting SOX7. Tumor Biology, 5(11), 10731–10736.

    Article  CAS  Google Scholar 

  109. Chen, L., Zhang, A., Li, Y., Zhang, K., Han, L., Du, W., et al. (2013). MiR-24 regulates the proliferation and invasion of glioma by ST7L via β-catenin/Tcf-4 signaling. Cancer Letters, 329(2), 174–180.

    Article  CAS  PubMed  Google Scholar 

  110. Rio-Machin, A., Ferreira, B. I., Henry, T., Gómez-López, G., Agirre, X., Alvarez, S., et al. (2013). Downregulation of specific miRNAs in hyperdiploid multiple myeloma mimics the oncogenic effect of IgH translocations occurring in the non-hyperdiploid subtype. Leukemia, 27(4), 925–931.

    Article  CAS  PubMed  Google Scholar 

  111. Du, W. W., Fang, L., Li, M., Yang, X., Liang, Y., Peng, C., et al. (2013). MicroRNA miR-24 enhances tumor invasion and metastasis by targeting PTPN9 and PTPRF to promote EGF signaling. Journal of Cell Science, 126(Pt 6), 1440–1453.

    Article  CAS  PubMed  Google Scholar 

  112. Xie, Y., Tobin, L. A., Camps, J., Wangsa, D., Yang, J., Rao, M., et al. (2013). MiR-24 regulates XIAP to reduce the apoptosis threshold in cancer cells. Oncogene, 32(19), 2442–2451.

    Article  CAS  PubMed  Google Scholar 

  113. Miao, Y., Li, J., Qiu, X., Li, Y., Wang, Z., & Luan, Y. (2013). miR-27a regulates the self renewal of the H446 small cell lung cancer cell line in vitro. Oncology Reports, 29(1), 161–168.

    CAS  PubMed  Google Scholar 

  114. Zhang, Z., Liu, S., Shi, R., & Zhao, G. (2011). miR-27 promotes human gastric cancer cell metastasis by inducing epithelial-to-mesenchymal transition. Cancer Genetics, 204, 486e491.

    Google Scholar 

  115. Wang, T., & Xu, Z. (2010). miR-27 promotes osteoblast differentiation by modulating Wnt signaling. Biochemical and Biophysical Research Communication, 402, 186–189.

    Article  CAS  Google Scholar 

  116. Salah, Z., Arafeh, R., Maximov, V., Galasso, M., Khawaled, S., Abou-Sharieha, S., et al. (2015). miR-27a and miR-27a* contribute to metastatic properties of osteosarcoma cells. Oncotarget, 6(7), 4920–4935.

    Article  PubMed  PubMed Central  Google Scholar 

  117. Guttilla, I. K., & White, B. A. (2009). Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells. Journal of Biological Chemistry, 284(35), 23204–23216.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Sun, B., Li, J., Shao, D., Pan, Y., Chen, Y., Li, S., et al. (2015). Adipose tissue-secreted miR-27a promotes liver cancer by targeting FOXO1 in obese individuals. Onco Targets and Therapy, 8, 735–744.

    Article  CAS  Google Scholar 

  119. Goto, Y., Kojima, S., Nishikawa, R., Enokida, H., Chiyomaru, T., Kinoshita, T., et al. (2014). The miR-23b/27b/24-1 cluster is a disease progression marker and tumor suppressor in prostate cancer. Oncotarget, 5(17), 7748–7759.

    Article  PubMed  PubMed Central  Google Scholar 

  120. Jiang, Y., Duan, Y., & Zhou, H. (2015). MicroRNA-27a directly targets KRAS to inhibit cell proliferation in esophageal squamous cell carcinoma. Oncology Letters, 9(1), 471–477.

    PubMed  Google Scholar 

  121. Zhu, L., Wang, Z., Fan, Q., Wang, R., & Sun, Y. (2014). MicroRNA-27a functions as a tumor suppressor in esophageal squamous cell carcinoma by targeting KRAS. Oncology Reports, 31(1), 280–286.

    CAS  PubMed  Google Scholar 

  122. Pan, W., Wang, H., Jianwei, R., & Ye, Z. (2014). MicroRNA-27a promotes proliferation, migration and invasion by targeting MAP2K4 in human osteosarcoma cells. Cellular Physiology and Biochemistry, 33, 402–412.

    Article  CAS  PubMed  Google Scholar 

  123. Zhao, X., Yang, L., & Hu, J. (2011). Down-regulation of miR-27a might inhibit proliferation and drug resistance of gastric cancer cells. Journal of Experimental & Clinical Cancer Research, 30, 55.

    Article  CAS  Google Scholar 

  124. Li, Z., Hu, S., Wang, J., Cai, J., Xiao, L., Yu, L., & Wang, Z. (2010). MiR-27a modulates MDR1/P-glycoprotein expression by targeting HIPK2 in human ovarian cancer cells. Gynecologic Oncology, 119(1), 125–130.

    Article  CAS  PubMed  Google Scholar 

  125. Zhang, H., Li, M., Han, Y., Hong, L., Gong, T., Sun, L., et al. (2010). Down-regulation of miR-27a might reverse multidrug resistance of esophageal squamous cell carcinoma. Digestive Diseases and Sciences, 55(9), 2545–2551.

    Article  CAS  PubMed  Google Scholar 

  126. Zhu, H., Wu, H., Liu, X., Evans, B. R., Medina, D. J., Liu, C. G., et al. (2008). Role of microRNA miR-27a and miR-451 in the regulation of MDR1/P-glycoprotein expression in human cancer cells. Biochemical Pharmacology, 76(5), 582–588.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Tian, Y., Fu, S., Qiu, G. B., Xu, Z. M., Liu, N., Zhang, X. W., et al. (2014). MicroRNA-27a promotes proliferation and suppresses apoptosis by targeting PLK2 in laryngeal carcinoma. BMC Cancer, 14, 678.

    Article  PubMed  PubMed Central  Google Scholar 

  128. Liu, T., Tang, H., Lang, Y., Liu, M., & Li, X. (2009). MiR-27a functions as an oncogene in gastric adenocarcinoma by targeting prohibitin. Cancer Letters, 273, 233–242.

    Article  CAS  PubMed  Google Scholar 

  129. Li, S., Li, J., Fei, B. Y., Shao, D., Pan, Y., Mo, Z. H., et al. (2015). MiR-27a promotes hepatocellular carcinoma cell proliferation through suppression of its target gene peroxisome proliferator-activated receptor γ. Chinese Medical Journal, 128(7), 941–947.

    Article  PubMed  PubMed Central  Google Scholar 

  130. Li, J., Wang, Y., Song, Y., Fu, Z., & Yu, W. (2014). miR-27a regulates cisplatin resistance and metastasis by targeting RKIP in human lung adenocarcinoma cells. Molecular Cancer, 13, 193.

    Article  PubMed  PubMed Central  Google Scholar 

  131. Jiang, J., Lv, X., Fan, L., Huang, G., Zhan, Y., Wang, M., & Lu, H. (2014). MicroRNA-27b suppresses growth and invasion of NSCLC cells by targeting Sp1. Tumor Biology, 35(10), 10019–10023.

    Article  CAS  PubMed  Google Scholar 

  132. Mertens-Talcott, S. U., Chintharlapalli, S., Li, X., & Safe, S. (2007). The oncogenic miR-27a targets genes that regulate specificity protein transcription factors and the G2-M checkpoint in MDA-MB-231 breast cancer cells. Cancer Research, 67(22), 11001–11011.

    Article  CAS  PubMed  Google Scholar 

  133. Bao, Y., Chen, Z., Guo, Y., Feng, Y., Li, Z., Han, W., et al. (2014). Tumor suppressor microRNA-27a in colorectal carcinogenesis and progression by targeting SGPP1 and Smad2. PLoS One, 9(8), e105991.

    Article  PubMed  PubMed Central  Google Scholar 

  134. Ma, Y., Yu, S., Zhao, W., Lu, Z., & Chen, J. (2010). miR-27a regulates the growth, colony formation and migration of pancreatic cancer cells by targeting Sprouty2. Cancer Letters, 298, 150–158.

    Article  CAS  PubMed  Google Scholar 

  135. Liu, C., Liang, S., Xiao, S., Lin, Q., Chen, X., Wu, Y., et al. (2015). MicroRNA-27b inhibits Spry2 expression and promotes cell invasion in glioma U251 cells. Oncology Letters, 9(3), 1393–1397.

    PubMed  PubMed Central  Google Scholar 

  136. Feng, J., Iwama, A., Satake, M., & Kohu, K. (2009). MicroRNA-27 enhances differentiation of myeloblasts into granulocytes by post-transcriptionally downregulating Runx1. British Journal of Haematology, 145, 412–423.

    Article  CAS  PubMed  Google Scholar 

  137. Jahid, S., Sun, J., Edwards, R. A., Dizon, D., Panarelli, N. C., Milsom, J. W., et al. (2012). miR-23a promotes the transition from indolent to invasive colorectal cancer. Cancer Discovery, 2(6), 540–553.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Chen, L., Li, H., Han, L., Zhang, K., Wang, G., Wang, Y., et al. (2011). Expression and function of miR-27b in human glioma. Oncology Reports, 26(6), 1617–1621.

    CAS  PubMed  Google Scholar 

  139. Naderi, E., Mostafaei, M., Pourshams, A., & Mohamadkhani, A. (2014). Network of microRNAs-mRNAs interactions in pancreatic cancer. BioMed Research International. doi:10.1155/2014/534821.

    PubMed  PubMed Central  Google Scholar 

  140. Guo, C., Deng, Y., Liu, J., & Qian, L. (2015). Cardiomyocyte-specific role of miR-24 in promoting cell survival. Journal of Cellular and Molecular Medicine, 19(1), 103–112.

    Article  CAS  PubMed  Google Scholar 

  141. Sun, L. Y., Wang, N., Ban, T., Sun, Y. H., Han, Y., Sun, L. L., et al. (2014). MicroRNA-23a mediates mitochondrial compromise in estrogen deficiency-induced concentric remodeling via targeting PGC-1α. Journal of Molecular and Cellular Cardiology, 75, 1–11.

    Article  CAS  PubMed  Google Scholar 

  142. Sabirzhanov, B., Zhao, Z., Stoica, B. A., Loane, D. J., Wu, J., Borroto, C., et al. (2014). Downregulation of miR-23a and miR-27a following experimental traumatic brain injury induces neuronal cell death through activation of proapoptotic Bcl-2 proteins. Journal of Neuroscience, 34(30), 10055–10071.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  143. Gibcus, J. H., Tan, L. P., Harms, G., Schakel, R. N., de Jong, D., Blokzijl, T., et al. (2009). Hodgkin lymphoma cell lines are characterized by a specific miR expression profile. Neoplasia, 11(2), 167–176.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Wang, Z., Wie, W., & Sarkar, F. H. (2012). miR-23a, a critical regulator of “migR”ation and metastasis in colorectal cancer. Cancer Discovery, 2(6), 489–491.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Cordero, F., Ferrero, G., Polidoro, S., Fiorito, G., Campanella, G., Sacerdote, C., et al. (2015). Differentially methylated miRs in prediagnostic samples of subjects who developed breast cancer in the European Prospective Investigation into Nutrition and Cancer (EPIC-Italy) cohort. Carcinogenesis, 36(10), 1144–1153.

    Article  PubMed  Google Scholar 

  146. Culpin, R. E., Sieniawski, M., Proctor, S. J., Menon, G., & Mainou-Fowler, T. (2013). MiRs are suitable for assessment as biomarkers from formalin-fixed paraffin-embedded tissue, and miR-24 represents an appropriate reference miR for diffuse large B-cell lymphoma studies. Journal of Clinical Pathology, 66(3), 249–252.

    Article  CAS  PubMed  Google Scholar 

  147. Yong, F. L., Law, C. W., & Wang, C. W. (2013). Potentiality of a triple miR classifier miR-193a-3p, miR-23a and miR-338-5p for early detection of colorectal cancer. BMC Cancer, 13, 280.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Tang, H. L., Deng, M., Liao, Q. J., Zeng, X., Zhou, X. T., & Su, Q. (2012). Expression and clinical significance of miR-23a and metastasis suppressor 1 in colon carcinoma. Zhonghua Bing Li Xue Za Zhi, 41(1), 28–32.

    CAS  PubMed  Google Scholar 

  149. Ogata-Kawata, H., Izumiya, M., Kurioka, D., Honma, Y., Yamada, Y., Furuta, K., et al. (2014). Circulating exosomal microRNAs as biomarkers of colon cancer. PLoS One, 9(4), e92921.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  150. Chen, G., Tang, Y., Wu, J. H., & Liu, F. H. (2014). Role of microRNAs in diagnosis and treatment of the pathogenesis of gastric cancer. International Journal of Clinical and Experimental Medicine, 7(12), 5947–5957.

    PubMed  PubMed Central  Google Scholar 

  151. Zhang, X. W., Liu, N., Chen, S., Wang, Y., Zhang, Z. X., Sun, Y. Y., et al. (2015). High miR-23a expression in laryngeal squamous cell carcinoma is associated with poor patient prognosis. Diagnostic Pathology, 10, 22.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  152. Eissa, S., Matboli, M., & Shehata, H. H. (2015). Breast tissue-based miR panel highlights miR-23a and selected target genes as putative biomarkers for breast cancer. Translational Research, 165(3), 417–427.

    Article  CAS  PubMed  Google Scholar 

  153. Wang, W. L., Yang, C., Han, X. L., Wang, R., Huang, Y., Zi, Y. M., et al. (2014). MicroRNA-23a expression in paraffin-embedded specimen correlates with overall survival of diffuse large B-cell lymphoma. Medical Oncology, 31(4), 919.

    Article  CAS  PubMed  Google Scholar 

  154. Ma, G., Dai, W., Sang, A., Yang, X., & Gao, C. (2014). Upregulation of miR-23a/b promotes tumor progression and confers poor prognosis in patients with gastric cancer. International Journal of Clinical and Experimental Pathology, 7(12), 8833–8840.

    PubMed  PubMed Central  Google Scholar 

  155. Li, X., Zhang, Y., Zhang, H., Liu, X., Gong, T., Li, M., et al. (2011). miR-223 promotes gastric cancer invasion and metastasis by targeting tumor suppressor EPB41L3. Molecular Cancer Research, 9(7), 824–833.

    Article  CAS  PubMed  Google Scholar 

  156. Bloomston, M., Frankel, W. L., Petrocca, F., Volinia, S., Alder, H., Hagan, J. P., et al. (2007). MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA, 297(17), 1901–1908.

    Article  CAS  PubMed  Google Scholar 

  157. Gattolliat, C. H., Uguen, A., Pesson, M., Trillet, K., Simon, B., Doucet, L., et al. (2015). MicroRNA and targeted mRNA expression profiling analysis in human colorectal adenomas and adenocarcinomas. European Journal of Cancer, 51(3), 409–420.

    Article  CAS  PubMed  Google Scholar 

  158. Eitan, R., Kushnir, M., Lithwick-Yanai, G., David, M. B., Hoshen, M., Glezerman, M., et al. (2009). Tumor microRNA expression patterns associated with resistance to platinum based chemotherapy and survival in ovarian cancer patients. Gynecologic Oncology, 114(2), 253–259.

    Article  CAS  PubMed  Google Scholar 

  159. Gottardo, F., Liu, C. G., Ferracin, M., Calin, G. A., Fassan, M., Bassi, P., et al. (2007). Micro-RNA profiling in kidney and bladder cancers. Urologic Oncology, 25(5), 387–392.

    Article  CAS  PubMed  Google Scholar 

  160. Park, Y. T., Jeong, J. Y., Lee, M. J., Kim, K. I., Kim, T. H., Kwon, Y. D., Lee, C., et al. (2013). MicroRNAs overexpressed in ovarian ALDH1-positive cells are associated with chemoresistance. Journal of Ovarian Research, 6(1), 18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Gao, Y., Liu, Y., Du, L., Li, J., Qu, A., Zhang, X., et al. (2015). Down-regulation of miR-24-3p in colorectal cancer is associated with malignant behavior. Medical Oncology, 32(1), 362.

    Article  PubMed  CAS  Google Scholar 

  162. Volinia, S., Calin, G. A., Liu, C. G., Ambs, S., Cimmino, A., Petrocca, F., et al. (2006). A miR expression signature of human solid tumors defines cancer gene targets. Proceedings of the National Academy of Sciences of the United States of America, 103(7), 2257–2261.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Meng, F. L., Wang, W., & Jia, W. D. (2014). Diagnostic and prognostic significance of serum miR-24-3p in HBV-related hepatocellular carcinoma. Medical Oncology, 31(9), 177.

    Article  PubMed  CAS  Google Scholar 

  164. Liu, Y. X., Long, X. D., Xi, Z. F., Ma, Y., Huang, X. Y., Yao, J. G., et al. (2014). MicroRNA-24 modulates aflatoxin B1-related hepatocellular carcinoma prognosis and tumorigenesis. BioMed Research International. doi:10.1155/2014/482926.

    Google Scholar 

  165. Salvi, A., Abeni, E., Portolani, N., Barlati, S., & De Petro, G. (2013). Human hepatocellular carcinoma cell-specific miRNAs reveal the differential expression of miR-24 and miR-27a in cirrhotic/non-cirrhotic HCC. International Journal of Oncology, 42(2), 391–402.

    CAS  PubMed  Google Scholar 

  166. Sochor, M., Basova, P., Pesta, M., Dusilkova, N., Bartos, J., Burda, P., et al. (2014). Oncogenic microRNAs, miR-155, miR-19a, miR-181b, and miR-24 enable monitoring of early breast cancer in serum. BMC Cancer, 14, 448.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  167. Yin, J. Y., Deng, Z. Q., Liu, F. Q., Qian, J., Lin, J., Tang, Q., et al. (2014). Association between mir-24 and mir-378 in formalin-fixed paraffin-embedded tissues of breast cancer. International Journal of Clinical and Experimental Pathology, 7(7), 4261–4267.

    PubMed  PubMed Central  Google Scholar 

  168. Franchina, T., Amodeo, V., Bronte, G., Savio, G., Ricciardi, G. R., Picciotto, M., et al. (2014). Circulating miR-22, miR-24 and miR-34a as novel predictive biomarkers to pemetrexed-based chemotherapy in advanced non-small cell lung cancer. Journal of Cellular Physiology, 229(1), 97–99.

    CAS  PubMed  Google Scholar 

  169. Le, H. B., Zhu, W. Y., Chen, D. D., He, J. Y., Huang, Y. Y., Liu, X. G., et al. (2012). Evaluation of dynamic change of serum miR-21 and miR-24 in pre- and post-operative lung carcinoma patients. Medical Oncology, 29(5), 3190–3197.

    Article  CAS  PubMed  Google Scholar 

  170. Xie, L., Wang, T., Yu, S., Chen, X., Wang, L., Qian, X., et al. (2011). Cell-free miR-24 and miR-30d, potential diagnostic biomarkers in malignant effusions. Clinical Biochemistry, 44, 216–220.

    Article  CAS  PubMed  Google Scholar 

  171. Yin, J. Y., Tang, Q., Qian, W., Qian, J., Lin, J., Wen, X. M., et al. (2014). Increased expression of miR-24 is associated with acute myeloid leukemia with t(8;21). International Journal of Clinical and Experimental Pathology, 7(11), 8032–8038.

    PubMed  PubMed Central  Google Scholar 

  172. Organista-Nava, J., Gómez-Gómez, Y., Illades-Aguiar, B., Del Carmen Alarcón-Romero, L., Saavedra-Herrera, M. V., Rivera-Ramírez, A. B., et al. (2015). High miR-24 expression is associated with risk of relapse and poor survival in acute leukemia. Oncology Reports, 33(4), 1639–1649.

    PubMed  PubMed Central  Google Scholar 

  173. Momen-Heravi, F., Trachtenberg, A. J., Kuo, W. P., & Cheng, Y. S. (2014). Genome-wide study of salivary microRNAs for detection of oral cancer. Journal of Dental Research, 93(7 Suppl), 86S–93S.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Tang, J., Zhao, H., Cai, H., & Wu, H. (2015). Diagnostic and prognostic potentials of microRNA-27a in osteosarcoma. Biomedicine & Pharmacotherapy, 71, 222–226.

    Article  CAS  Google Scholar 

  175. Tang, W., Zhu, J., Su, S., Wu, W., Liu, Q., Su, F., et al. (2012). MiR-27 as a prognostic marker for breast cancer progression and patient survival. PLoS One, 7(12), e51702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Mozos, A., Catasús, L., D’Angelo, E., Serrano, E., Espinosa, I., Ferrer, I., et al. (2014). The FOXO1-miR27 tandem regulates myometrial invasion in endometrioid endometrial adenocarcinoma. Human Pathology, 45(5), 942–951.

    Article  CAS  PubMed  Google Scholar 

  177. Peng, H., Wang, X., Zhang, P., Sun, T., Ren, X., & Xia, Z. (2015). miR-27a promotes cell proliferation and metastasis in renal cell carcinoma. International Journal of Clinical and Experimental Pathology, 8(2), 2259–2266.

    CAS  PubMed  PubMed Central  Google Scholar 

  178. Heegaard, N. H., Schetter, A. J., Welsh, J. A., Yoneda, M., Bowman, E. D., & Harris, C. C. (2012). Circulating micro-RNA expression profiles in early stage non-small cell lung cancer. International Journal of Cancer, 130(6), 1378–1386.

    Article  CAS  PubMed  Google Scholar 

  179. Zhang, B., Pan, X., Cobb, G. P., & Anderson, T. A. (2007). miRs as oncogenes and tumor suppressors. Developmental Biology, 302, 1–12.

    Article  CAS  PubMed  Google Scholar 

  180. Aparicio, L. A., Blanco, M., Castosa, R., Concha, Á., Valladares, M., Calvo, L., et al. (2015). Clinical implications of epithelial cell plasticity in cancer progression. Cancer Letters, 366(1), 1–10.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work is supported by the European Union under the framework FP7 (JH, AS) and the German Research Foundation (RH, CM).

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  1. University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Martinistr. 52, Building O24, 20246, Hamburg, Germany

    Jörg Haier

  2. Comprehensive Cancer Center Münster (CCCM), University Hospital Münster, Münster, Germany

    Anda Ströse, Christiane Matuszcak & Richard Hummel

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  1. Jörg Haier
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  2. Anda Ströse
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  3. Christiane Matuszcak
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  4. Richard Hummel
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Correspondence to Jörg Haier.

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Haier, J., Ströse, A., Matuszcak, C. et al. miR clusters target cellular functional complexes by defining their degree of regulatory freedom. Cancer Metastasis Rev 35, 289–322 (2016). https://doi.org/10.1007/s10555-016-9617-1

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