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MicroRNAs in cancer diagnosis and therapy: from bench to bedside

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Abstract

Epigenetic changes, such as DNA methylation and histone modifications, regulate gene expression. It is speculated that investigating the fundamental epigenetic mechanisms and their gene regulation will promote a better understanding of cancer development. The idea of epigenetic modification has been extended to microRNAs (miRs). MiRs are single-stranded RNA molecules, about 19–25 ribonucleotides in length, which regulate gene expression post-transcriptionally and can act as tumor suppressors or oncogenes. We review the most recent findings related to their mechanisms of action, the modification of miR expression, and their relationship to cancer. We also discuss the potential application of miRs in the clinical setting, such as for biomarkers and therapy.

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References

  1. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70.

    Article  PubMed  CAS  Google Scholar 

  2. Maser RS, DePinho RA. Connecting chromosomes, crisis, and cancer. Science. 2002;297:565–9.

    Article  PubMed  CAS  Google Scholar 

  3. Holliday R. Epigenetics: a historical overview. Epigenetics. 2006;1:76–80.

    Article  PubMed  Google Scholar 

  4. Brait M, Sidransky D. Cancer epigenetics: above and beyond. Toxicol Mech Methods. 2011;21:275–88.

    Article  PubMed  CAS  Google Scholar 

  5. Baccarelli A, Bollati V. Epigenetics and environmental chemicals. Curr Opin Pediatr. 2009;21:243–51.

    Article  PubMed  Google Scholar 

  6. Deaton AM, Bird A. CpG islands and the regulation of transcription. Genes Dev. 2011;25:1010–22.

    Article  PubMed  CAS  Google Scholar 

  7. Hatziapostolou M, Iliopoulos D. Epigenetic aberrations during oncogenesis. Cell Mol Life Sci. 2011;68:1681–702.

    Article  PubMed  CAS  Google Scholar 

  8. Hoshino I, Matsubara H. Recent advances in histone deacetylase targeted cancer therapy. Surg Today. 2010;40:809–15.

    Article  PubMed  CAS  Google Scholar 

  9. Lewandowska J, Bartoszek A. DNA methylation in cancer development, diagnosis and therapy—multiple opportunities for genotoxic agents to act as methylome disruptors or remediators. Mutagenesis. 2011;26:475–87.

    Article  PubMed  CAS  Google Scholar 

  10. Wu SC, Zhang Y. Active DNA demethylation: many roads lead to Rome. Nat Rev Mol Cell Biol. 2010;11:607–20.

    Article  PubMed  CAS  Google Scholar 

  11. Wild L, Flanagan JM. Genome-wide hypomethylation in cancer may be a passive consequence of transformation. Biochim Biophys Acta. 2010;1806:50–7.

    PubMed  CAS  Google Scholar 

  12. Jelinic P, Shaw P. Loss of imprinting and cancer. J Pathol. 2007;211:261–8.

    Article  PubMed  CAS  Google Scholar 

  13. Sansom OJ, Maddison K, Clarke AR. Mechanisms of disease: methyl-binding domain proteins as potential therapeutic targets in cancer. Nat Clin Pract Oncol. 2007;4:305–15.

    Article  PubMed  CAS  Google Scholar 

  14. Kaminskas E, Farrell AT, Wang YC, Sridhara R, Pazdur R. FDA drug approval summary: azacitidine (5-azacytidine, Vidaza) for injectable suspension. Oncologist. 2005;10:176–82.

    Article  PubMed  CAS  Google Scholar 

  15. Stathis A, Hotte SJ, Chen EX, et al. Phase I study of decitabine in combination with vorinostatin patients with advanced solid tumors and non-Hodgkin’s lymphomas. Clin Cancer Res. 2011;15(17):1582–90.

    Article  Google Scholar 

  16. Sekeres MA, O’Keefe C, List AF, Paulic K, Afable M 2nd, Englehaupt R, Maciejewski JP. Demonstration of additional benefit in adding lenalidomide to azacitidine in patients with higher-risk myelodysplastic syndromes. Am J Hematol. 2011;86:102–3.

    Article  PubMed  Google Scholar 

  17. Fu S, Hu W, Iyer R, Kavanagh JJ, et al. Phase 1b-2a study to reverse platinum resistance through use of a hypomethylating agent, azacitidine, in patients with platinum-resistant or platinum-refractory epithelial ovarian cancer. Cancer. 2011;117:1661–9.

    Article  PubMed  CAS  Google Scholar 

  18. Garcia-Manero G, Gore SD, Cogle C, et al. Phase I study of oral azacitidine in myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia. J Clin Oncol. 2011;29:2521–7.

    Article  PubMed  CAS  Google Scholar 

  19. Hake SB, Xiao A, Allis CD. Linking the epigenetic ‘language’ of covalent histone modifications to cancer. Br J Cancer. 2004;90:761–9.

    Article  PubMed  CAS  Google Scholar 

  20. Jenuwein T, Allis CD. Translating the histone code. Science. 2001;293:1074–80.

    Article  PubMed  CAS  Google Scholar 

  21. Varier RA, Timmers HT. Histone lysine methylation and demethylation pathways in cancer. Biochim Biophys Acta. 2011;1815:75–89.

    PubMed  CAS  Google Scholar 

  22. Sawan C, Herceg Z. Histone modifications and cancer. Adv Genet. 2010;70:57–85.

    Article  PubMed  CAS  Google Scholar 

  23. Lafon-Hughes L, Di Tomaso MV, Méndez-Acuña L, Martínez-López W. Chromatin-remodelling mechanisms in cancer. Mutat Res. 2008;658:191–214.

    Article  PubMed  CAS  Google Scholar 

  24. Mitsiades CS, Mitsiades NS, McMullan CJ, et al. Transcriptional signature of histone deacetylase inhibition in multiple myeloma: biological and clinical implications. Proc Natl Acad Sci USA. 2004;101:540–5.

    Article  PubMed  CAS  Google Scholar 

  25. Bacon AL, Fox S, Turley H, Harris AL. Selective silencing of the hypoxia-inducible factor 1 target gene BNIP3 by histone deacetylation and methylation in colorectal cancer. Oncogene. 2007;26:132–41.

    Article  PubMed  CAS  Google Scholar 

  26. Hoshino I, Matsubara H, Hanari N, et al. Histone deacetylase inhibitor FK228 activates tumor suppressor Prdx1 with apoptosis induction in esophageal cancer cells. Clin Cancer Res. 2005;11:7945–52.

    Article  PubMed  CAS  Google Scholar 

  27. Duvic M, Talpur R, Ni X, et al. Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL). Blood. 2007;109:31–9.

    Article  PubMed  CAS  Google Scholar 

  28. Whittaker SJ, Demierre MF, Kim EJ, et al. Final results from a multicenter, international, pivotal study of romidepsin in refractory cutaneous T-cell lymphoma. J Clin Oncol. 2010;28:4485–91.

    Article  PubMed  CAS  Google Scholar 

  29. Fujiwara Y, Yamamoto N, Yamada Y, et al. Phase I and pharmacokinetic study of vorinostat (suberoylanilide hydroxamic acid) in Japanese patients with solid tumors. Cancer Sci. 2009;100:1728–34.

    Article  PubMed  CAS  Google Scholar 

  30. Munster PN, Marchion D, Thomas S, et al. Phase I trial of vorinostat and doxorubicin in solid tumours: histone deacetylase 2 expression as a predictive marker. Br J Cancer. 2009;101:1044–50.

    Article  PubMed  CAS  Google Scholar 

  31. Bertino EM, Otterson GA. Romidepsin: a novel histone deacetylase inhibitor for cancer. Expert Opin Investig Drugs. 2011;20:1151–8.

    Article  PubMed  CAS  Google Scholar 

  32. Esteller M. Non-coding RNAs in human disease. Nat Rev Genet. 2011;12:861–74.

    Article  PubMed  CAS  Google Scholar 

  33. Yekta S, Shih IH, Bartel DP. MicroRNA-directed cleavage of HOXB8 mRNA. Science. 2004;304:594–6.

    Article  PubMed  CAS  Google Scholar 

  34. van Kouwenhove M, Kedde M, Agami R. MicroRNA regulation by RNA-binding proteins and its implications for cancer. Nat Rev Cancer. 2011;11:644–56.

    Article  PubMed  CAS  Google Scholar 

  35. Liu CG, Spizzo R, Calin GA, Croce CM. Expression profiling of microRNA using oligo DNA arrays. Methods. 2008;44(1):22–30.

    Article  PubMed  CAS  Google Scholar 

  36. Kukreja RC, Yin C, Salloum FN. MicroRNAs: new players in cardiac injury and protection. Mol Pharmacol. 2011;80:558–64.

    Article  PubMed  CAS  Google Scholar 

  37. Liu NK, Xu XM. MicroRNA in central nervous system trauma and degenerative disorders. Physiol Genomics. 2011;43:571–80.

    Article  PubMed  CAS  Google Scholar 

  38. Corcoran DL, Pandit KV, Gordon B, Bhattacharjee A, Kaminski N, Benos PV. Features of mammalian microRNA promoters emerge from polymerase II chromatin immunoprecipitation data. PLoS One. 2009;4:e5279.

    Article  PubMed  CAS  Google Scholar 

  39. Bortolin-Cavaillé ML, Dance M, Weber M, Cavaillé J. C19MC microRNAs are processed from introns of large Pol-II, non-protein-coding transcripts. Nucleic Acids Res. 2009;37:3464–73.

    Article  PubMed  CAS  Google Scholar 

  40. Pacifico F, Crescenzi E, Mellone S, et al. Nuclear factor-{kappa}B contributes to anaplastic thyroid carcinomas through up-regulation of miR-146a. J Clin Endocrinol Metab. 2010;95:1421–30.

    Article  PubMed  CAS  Google Scholar 

  41. Monteys AM, Spengler RM, Wan J, et al. Structure and activity of putative intronic miRNA promoters. RNA. 2010;16:495–505.

    Article  PubMed  Google Scholar 

  42. Lee J, Li Z, Brower-Sinning R, John B. Regulatory circuit of human microRNA biogenesis. PLoS Comput Biol. 2007;3:e67.

    Article  PubMed  CAS  Google Scholar 

  43. Rota R, Ciarapica R, Giordano A, Miele L, Locatelli F. MicroRNAs in rhabdomyosarcoma: pathogenetic implications and translational potentiality. Mol Cancer. 2011;10:120.

    Article  PubMed  CAS  Google Scholar 

  44. Sun G, Yan J, Noltner K, Feng J, Li H, Sarkis DA, Sommer SS, Rossi JJ. SNPs inhuman miRNA genes affect biogenesis and function. RNA. 2009;15:1640–51.

    Article  PubMed  CAS  Google Scholar 

  45. Brennecke J, Stark A, Russell RB, Cohen SM. Principles of microRNA-target recognition. PLoS Biol. 2005;3:e85.

    Article  PubMed  CAS  Google Scholar 

  46. Robertson B, Dalby AB, Karpilow J, Khvorova A, Leake D, Vermeulen A. Specificity and functionality of microRNA inhibitors. Silence. 2010;1:10.

    Article  PubMed  CAS  Google Scholar 

  47. Yang Z, Wang L. Regulation of microRNA expression and function by nuclear receptor signaling. Cell Biosci. 2011;1:31.

    Article  PubMed  CAS  Google Scholar 

  48. Ørom UA, Nielsen FC, Lund AH. MicroRNA-10a binds the 5′UTR of ribosomal protein mRNAs and enhances their translation. Mol Cell. 2008;30:460–71.

    Article  PubMed  CAS  Google Scholar 

  49. Place RF, Li LC, Pookot D, Noonan EJ, Dahiya R. MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc Natl Acad Sci USA. 2008;105:1608–13.

    Article  PubMed  CAS  Google Scholar 

  50. Sato F, Tsuchiya S, Meltzer SJ, Shimizu K. MicroRNAs and epigenetics. FEBS J. 2011;278:1598–609.

    Article  PubMed  CAS  Google Scholar 

  51. Silahtaroglu A, Stenvang J. MicroRNAs, epigenetics and disease. Essays Biochem. 2010;48:165–85.

    Article  PubMed  CAS  Google Scholar 

  52. Melo SA, Esteller M. Dysregulation of microRNAs in cancer: playing with fire. FEBS Lett. 2011;585:2087–99.

    Article  PubMed  CAS  Google Scholar 

  53. Lujambio A, Esteller M. CpG island hypermethylation of tumor suppressor microRNAs in human cancer. Cell Cycle. 2007;6:1455–9.

    Article  PubMed  CAS  Google Scholar 

  54. Esteller M. Epigenetic gene silencing in cancer: the DNA hypermethylome. Hum Mol Genet. 2007;16:R50–9.

    Article  PubMed  CAS  Google Scholar 

  55. Tang JT, Fang JY. MicroRNA regulatory network in human colorectal cancer. Mini Rev Med Chem. 2009;9:921–6.

    Article  PubMed  CAS  Google Scholar 

  56. Fraga MF, Esteller M. Towards the human cancer epigenome: a first draft of histone modifications. Cell Cycle. 2005;4:1377–81.

    Article  PubMed  CAS  Google Scholar 

  57. Maekawa M, Watanabe Y. Epigenetics: relations to disease and laboratory findings. Curr Med Chem. 2007;14:2642–53.

    Article  PubMed  CAS  Google Scholar 

  58. Fazi F, Racanicchi S, Zardo G, Starnes LM, Mancini M, Travaglini L, et al. Epigenetic silencing of the myelopoiesis regulator microRNA-223 by the AML1/ETO oncoprotein. Cancer Cell. 2007;12:457–66.

    Article  PubMed  CAS  Google Scholar 

  59. O’Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulated microRNAs modulate E2F1 expression. Nature. 2005;435:839–43.

    Article  PubMed  CAS  Google Scholar 

  60. He L, He X, Lim LP, de Stanchina E, Xuan Z, Liang Y, et al. A microRNA component of the p53 tumour suppressor network. Nature. 2007;447:1130–4.

    Article  PubMed  CAS  Google Scholar 

  61. Giannakakis A, Sandaltzopoulos R, Greshock J, Liang S, Huang J, Hasegawa K, et al. miR-210 links hypoxia with cell cycle regulation and is deleted in human epithelial ovarian cancer. Cancer Biol Ther. 2008;7:255–64.

    Article  PubMed  CAS  Google Scholar 

  62. Calin GA, Liu CG, Sevignani C, Ferracin M, Felli N, Dumitru CD, et al. MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci USA. 2004;101:11755–60.

    Article  PubMed  CAS  Google Scholar 

  63. Raveche ES, Salerno E, Scaglione BJ, Manohar V, Abbasi F, Lin YC, et al. Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice. Blood. 2007;109:5079–86.

    Article  PubMed  CAS  Google Scholar 

  64. Diederichs S, Haber DA. Sequence variations of microRNAs in human cancer: alterations in predicted secondary structure do not affect processing. Cancer Res. 2006;66:6097–104.

    Article  PubMed  CAS  Google Scholar 

  65. Pinkel D, Albertson DG. Array comparative genomic hybridization and its applications in cancer. Nat Genet. 2005;37(Suppl):S11–7.

    Article  PubMed  CAS  Google Scholar 

  66. Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, 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. 2002;99:15524–9.

    Article  PubMed  CAS  Google Scholar 

  67. Zhang L, Volinia S, Bonome T, Calin GA, Greshock J, Yang N, et al. Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer. Proc Natl Acad Sci USA. 2008;105:7004–9.

    Article  PubMed  CAS  Google Scholar 

  68. Medina PP, Slack FJ. microRNAs and cancer: an overview. Cell Cycle. 2008;7:2485–92.

    Article  PubMed  CAS  Google Scholar 

  69. Tie J, Fan D. Big roles of microRNAs in tumorigenesis and tumor development. Histol Histopathol. 2011;26:1353–61.

    PubMed  CAS  Google Scholar 

  70. Nohata N, Hanazawa T, Seki N, et al. Tumor suppressive microRNA-375 regulates oncogene AEG-1/MTDH in head and neck squamous cell carcinoma (HNSCC). J Hum Genet. 2011;56:595–601.

    Article  PubMed  CAS  Google Scholar 

  71. Li X, Lin R, Li J. Epigenetic silencing of microRNA-375 regulates PDK1 expression in esophageal cancer. Dig Dis Sci. 2011;56:2849–56.

    Google Scholar 

  72. Tsukamoto Y, Nakada C, Moriyama M, et al. MicroRNA-375 is downregulated in gastric carcinomas and regulates cell survival by targeting PDK1 and 14-3-3ζ. Cancer Res. 2010;70:2339–49.

    Article  PubMed  CAS  Google Scholar 

  73. LaConti JJ, Shivapurkar N, Preet A, et al. Tissue and serum microRNAs in the Kras(G12D) transgenic animal model and in patients with pancreatic cancer. PLoS One. 2011;6(6):e20687.

    Article  PubMed  CAS  Google Scholar 

  74. He XX, Chang Y, Meng FY, Wang MY, et al. MicroRNA-375 targets AEG-1 in hepatocellular carcinoma and suppresses liver cancer cell growth in vitro and in vivo. Oncogene. 2012;31:3357–69.

    Google Scholar 

  75. Kong KL, Kwong DL, Chan TH, et al. MicroRNA-375 inhibits tumour growth and metastasis in oesophageal squamous cell carcinoma through repressing insulin-like growth factor 1 receptor. Gut. 2012;61:33–42.

    Article  PubMed  CAS  Google Scholar 

  76. Mazar J, DeBlasio D, Govindarajan SS, Zhang S, Perera RJ. Epigenetic regulation of microRNA-375 and its role in melanoma development in humans. FEBS Lett. 2011;585:2467–76.

    Article  PubMed  CAS  Google Scholar 

  77. Yang X, Cao W, Zhou J, et al. 14-3-3Zeta positive expression is associated with a poor prognosis in patients with glioblastoma. Neurosurgery. 2011;68:932–8.

    PubMed  Google Scholar 

  78. Neal CL, Yu D. 14-3-3Zeta as a prognostic marker and therapeutic target for cancer. Expert Opin Ther Targets. 2010;14:1343–54.

    Article  PubMed  CAS  Google Scholar 

  79. Neal CL, Yao J, Yang W, et al. 14-3-3zeta overexpression defines high risk for breast cancer recurrence and promotes cancer cell survival. Cancer Res. 2009;15(69):3425–32.

    Article  CAS  Google Scholar 

  80. Chen W, Ke Z, Shi H, Yang S, Wang L. Overexpression of AEG-1 in renal cell carcinoma and its correlation with tumor nuclear grade and progression. Neoplasma. 2010;57:522–9.

    Article  PubMed  CAS  Google Scholar 

  81. Li C, Li R, Song H, Wang D, et al. Significance of AEG-1 expression in correlation with VEGF, microvessel density and clinicopathological characteristics in triple-negative breast cancer. J Surg Oncol 2010.

  82. Li C, Li R, Song H, Wang D, et al. Significance of AEG-1 expression in correlation with VEGF, microvessel density and clinicopathological characteristics in triple-negative breast cancer. J Surg Oncol. 2011;103:184–92.

    Article  PubMed  CAS  Google Scholar 

  83. Meng F, Luo C, Ma L, Hu Y, Lou G. Clinical significance of astrocyte elevated gene-1 expression in human epithelial ovarian carcinoma. Int J Gynecol Pathol. 2011;30:145–50.

    Article  PubMed  Google Scholar 

  84. Song H, Li C, Lu R, Zhang Y, Geng J. Expression of astrocyte elevated gene-1: a novel marker of the pathogenesis, progression, and poor prognosis for endometrial cancer. Int J Gynecol Cancer. 2010;20:1188–96.

    Article  PubMed  Google Scholar 

  85. Akao Y, Nakagawa Y, Naoe T. let-7 microRNA functions as a potential growth suppressor in human colon cancer cells. Biol Pharm Bull. 2006;29:903–6.

    Article  PubMed  CAS  Google Scholar 

  86. Esquela-Kerscher A, Trang P, et al. The let-7 microRNA reduces tumor growth in mouse models of lung cancer. Cell Cycle. 2008;7:759–64.

    Article  PubMed  CAS  Google Scholar 

  87. Ricarte-Filho JC, Fuziwara CS, Yamashita AS, Rezende E, da-Silva MJ, Kimura ET. Effects of let-7 microRNA on cell growth and differentiation of papillary thyroid cancer. Transl Oncol. 2009;2:236–41.

    PubMed  Google Scholar 

  88. Dong Q, Meng P, Wang T, et al. MicroRNA let-7a inhibits proliferation of human prostate cancer cells in vitro and in vivo by targeting E2F2 and CCND2. PLoS One. 2010;5:e10147.

    Article  PubMed  CAS  Google Scholar 

  89. Lee ST, Chu K, Oh HJ, et al. Let-7 microRNA inhibits the proliferation of human glioblastoma cells. J Neurooncol. 2011;102:19–24.

    Article  PubMed  CAS  Google Scholar 

  90. Yu CC, Chen YW, Chiou GY, et al. MicroRNA let-7a represses chemoresistance and tumourigenicity in head and neck cancer via stem-like properties ablation. Oral Oncol. 2011;47:202–10.

    Article  PubMed  CAS  Google Scholar 

  91. Boyerinas B, Park SM, Hau A, Murmann AE, Peter ME. The role of let-7 in cell differentiation and cancer. Endocr Relat Cancer. 2010;17:F19–36.

    Article  PubMed  CAS  Google Scholar 

  92. Barh D, Malhotra R, Ravi B, Sindhurani P. MicroRNA let-7: an emerging next-generation cancer therapeutic. Curr Oncol. 2010;17:70–80.

    Article  PubMed  CAS  Google Scholar 

  93. Childs G, Fazzari M, Kung G, Kawachi N, et al. Low-level expression of microRNAs let-7d and miR-205 are prognostic markers of head and neck squamous cell carcinoma. Am J Pathol. 2009;174:736–45.

    Article  PubMed  CAS  Google Scholar 

  94. Helland Å, Anglesio MS, George J, et al. Deregulation of MYCN, LIN28B and LET7 in a molecular subtype of aggressive high-grade serous ovarian cancers. PLoS One. 2011;6(4):e18064.

    Article  PubMed  CAS  Google Scholar 

  95. Watanabe S, Ueda Y, Akaboshi S, Hino Y, Sekita Y, Nakao M. HMGA2 maintains oncogenic RAS-induced epithelial-mesenchymal transition in human pancreatic cancer cells. Am J Pathol. 2009;174:854–68.

    Article  PubMed  CAS  Google Scholar 

  96. Yu F, Yao H, Zhu P, Zhang X, et al. let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell. 2007;131:1109–23.

    Article  PubMed  CAS  Google Scholar 

  97. He L, He X, Lowe SW, Hannon GJ. microRNAs join the p53 network—another piece in the tumour-suppression puzzle. Nat Rev Cancer. 2007;7:819–22.

    Article  PubMed  CAS  Google Scholar 

  98. Hermeking H. The miR-34 family in cancer and apoptosis. Cell Death Differ. 2010;17:193–9.

    Article  PubMed  CAS  Google Scholar 

  99. Gallardo E, Navarro A, Viñolas N, et al. miR-34a as a prognostic marker of relapse in surgically resected non-small-cell lung cancer. Carcinogenesis. 2009;30:1903–9.

    Article  PubMed  CAS  Google Scholar 

  100. O’Day E, Lal A. MicroRNAs and their target gene networks in breast cancer. Breast Cancer Res. 2010;12:201.

    Article  PubMed  CAS  Google Scholar 

  101. Corney DC, Hwang CI, Matoso A, et al. Frequent downregulation of miR-34 family in human ovarian cancers. Clin Cancer Res. 2010;16:1119–28.

    Article  PubMed  CAS  Google Scholar 

  102. Yamakuchi M, Ferlito M, Lowenstein CJ. miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci USA. 2008;105:13421–6.

    Article  PubMed  CAS  Google Scholar 

  103. Vogt M, Munding J, Grüner M, et al. Frequent concomitant inactivation of miR-34a and miR-34b/c by CpG methylation in colorectal, pancreatic, mammary, ovarian, urothelial, and renal cell carcinomas and soft tissue sarcomas. Virchows Arch. 2011;458:313–22.

    Article  PubMed  Google Scholar 

  104. Mudduluru G, Ceppi P, Kumarswamy R, Scagliotti GV, Papotti M, Allgayer H. Regulation of Axl receptor tyrosine kinase expression by miR-34a and miR-199a/b in solid cancer. Oncogene. 2011;30:2888–99.

    Article  PubMed  CAS  Google Scholar 

  105. Wang Z, Chen Z, Gao Y, et al. DNA hypermethylation of microRNA-34b/c has prognostic value for stage I non-small cell lung cancer. Cancer Biol Ther. 2011;11:490–6.

    Article  PubMed  CAS  Google Scholar 

  106. Tanaka N, Toyooka S, Soh J, et al. Frequent methylation and oncogenic role of microRNA-34b/c in small-cell lung cancer. Lung Cancer. 2012;76:32–8.

    Google Scholar 

  107. Wong KY, Yu L, Chim CS. DNA methylation of tumor suppressor miRNA genes: a lesson from the miR-34 family. Epigenomics. 2011;3:83–92.

    Article  PubMed  CAS  Google Scholar 

  108. Antonini D, Russo MT, De Rosa L, Gorrese M, Del Vecchio L, Missero C. Transcriptional repression of miR-34 family contributes to p63-mediated cellcycle progression in epidermal cells. J Invest Dermatol. 2010;130:1249–57.

    Article  PubMed  CAS  Google Scholar 

  109. Ji Q, Hao X, Meng Y, Zhang M, Desano J, Fan D, Xu L. Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres. BMC Cancer. 2008;8:266.

    Article  PubMed  CAS  Google Scholar 

  110. Chang TC, Wentzel EA, Kent OA, et al. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell. 2007;26:745–52.

    Article  PubMed  CAS  Google Scholar 

  111. Raver-Shapira N, Marciano E, Meiri E, et al. Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell. 2007;26:731–43.

    Article  PubMed  CAS  Google Scholar 

  112. Bommer GT, Gerin I, Feng Y, et al. p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr Biol. 2007;17:1298–307.

    Article  PubMed  CAS  Google Scholar 

  113. Yamakuchi M, Lowenstein CJ. MiR-34, SIRT1 and p53: the feedback loop. Cell Cycle. 2009;8:712–5.

    Article  PubMed  CAS  Google Scholar 

  114. Krutovskikh VA, Herceg Z. Oncogenic microRNAs (OncomiRs) as a new class of cancer biomarkers. Bioessays. 2010;32:894–904.

    Article  PubMed  CAS  Google Scholar 

  115. Reshmi G, Pillai MR. Beyond HPV: oncomirs as new players in cervical cancer. FEBS Lett. 2008;582:4113–6.

    Article  PubMed  CAS  Google Scholar 

  116. Medina PP, Nolde M, Slack FJ. OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma. Nature. 2010;467:86–90.

    Article  PubMed  CAS  Google Scholar 

  117. Wong AM, Kong KL, Tsang JW, Kwong DL, Guan XY. Profiling of Epstein-Barr virus-encoded microRNAs in nasopharyngeal carcinoma reveals potential biomarkers and oncomirs. Cancer. 2012;118:698–710.

    Google Scholar 

  118. Iorio MV, Ferracin M, Liu CG, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65:7065–70.

    Article  PubMed  CAS  Google Scholar 

  119. Schetter AJ, Leung SY, Sohn JJ, et al. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 2008;299:425–36.

    Article  PubMed  CAS  Google Scholar 

  120. Dillhoff M, Liu J, Frankel W, Croce C, Bloomston M. MicroRNA-21 is overexpressed in pancreatic cancer and a potential predictor of survival. J Gastrointest Surg. 2008;12:2171–6.

    Article  PubMed  Google Scholar 

  121. Markou A, Tsaroucha EG, Kaklamanis L, Fotinou M, Georgoulias V, Lianidou ES. Prognostic value of mature microRNA-21 and microRNA-205 overexpression in non-small cell lung cancer by quantitative real-time RT-PCR. Clin Chem. 2008;54:1696–704.

    Article  PubMed  CAS  Google Scholar 

  122. Connolly E, Melegari M, Landgraf P, et al. Elevated expression of the miR-17-92 polycistron and miR-21 in hepadnavirus-associated hepatocellular carcinoma contributes to the malignant phenotype. Am J Pathol. 2008;173:856–64.

    Article  PubMed  CAS  Google Scholar 

  123. Chan SH, Wu CW, Li AF, Chi CW, Lin WC. miR-21 microRNA expression in human gastric carcinomas and its clinical association. Anticancer Res. 2008;28:907–11.

    PubMed  Google Scholar 

  124. Feber A, Xi L, Luketich JD, Pennathur A, et al. MicroRNA expression profiles of esophageal cancer. J Thorac Cardiovasc Surg. 2008;135:255–60.

    Article  PubMed  CAS  Google Scholar 

  125. Li J, Huang H, Sun L, Yang M, et al. MiR-21 indicates poor prognosis in tongue squamous cell carcinomas as an apoptosis inhibitor. Clin Cancer Res. 2009;15:3998–4008.

    Article  PubMed  CAS  Google Scholar 

  126. Selaru FM, Olaru AV, Kan T, et al. MicroRNA-21 is overexpressed in human cholangiocarcinoma and regulates programmed cell death 4 and tissue inhibitor of metalloproteinase 3. Hepatology. 2009;49:1595–601.

    Article  PubMed  CAS  Google Scholar 

  127. Lakomy R, Sana J, Hankeova S, et al. MiR-195, miR-196b, miR-181c, miR-21 expression levels and O-6-methylguanine-DNA methyltransferase methylation status are associated with clinical outcome in glioblastoma patients. Cancer Sci. 2011;102:2186–90.

    Article  PubMed  CAS  Google Scholar 

  128. Folini M, Gandellini P, Longoni N, et al. miR-21: an oncomir on strike in prostate cancer. Mol Cancer. 2010;9:12.

    Article  PubMed  CAS  Google Scholar 

  129. Mei M, Ren Y, Zhou X, et al. Downregulation of miR-21 enhances chemotherapeutic effect of taxol in breast carcinoma cells. Technol Cancer Res Treat. 2010;9:77–86.

    PubMed  CAS  Google Scholar 

  130. Corsten MF, Miranda R, Kasmieh R, Krichevsky AM, Weissleder R, Shah K. MicroRNA-21 knockdown disrupts glioma growth in vivo and displays synergistic cytotoxicity with neural precursor cell delivered S-TRAIL in human gliomas. Cancer Res. 2007;67:8994–9000.

    Article  PubMed  CAS  Google Scholar 

  131. Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007;133:647–58.

    Article  PubMed  CAS  Google Scholar 

  132. Zhang S, Yu D. PI(3)king apart PTEN’s role in cancer. Clin Cancer Res. 2010;16:4325–30.

    Article  PubMed  CAS  Google Scholar 

  133. Tran N, McLean T, Zhang X, et al. MicroRNA expression profiles in head and neck cancer cell lines. Biochem Biophys Res Commun. 2007;358:12–7.

    Article  PubMed  CAS  Google Scholar 

  134. Zhu S, Si ML, Wu H, Mo YY. MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem. 2007;282:14328–36.

    Article  PubMed  CAS  Google Scholar 

  135. Schramedei K, Mörbt N, Pfeifer G, et al. MicroRNA-21 targets tumor suppressor genes ANP32A and SMARCA4. Oncogene. 2011;30:2975–85.

    Article  PubMed  CAS  Google Scholar 

  136. Zhou R, Hu G, Gong AY, Chen XM. Binding of NF-kappaB p65 subunit to the promoter elements is involved in LPS-induced transactivation of miRNA genes in human biliary epithelial cells. Nucleic Acids Res. 2010;38:3222–32.

    Article  PubMed  CAS  Google Scholar 

  137. Voorhoeve PM, le Sage C, Schrier M, et al. A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell. 2006;124:1169–81.

    Article  PubMed  CAS  Google Scholar 

  138. Yang K, Handorean AM, Iczkowski KA. MicroRNAs 373 and 520c are downregulated in prostate cancer, suppress CD44 translation and enhance invasion of prostate cancer cells in vitro. Int J Clin Exp Pathol. 2009;2:361–9.

    PubMed  CAS  Google Scholar 

  139. Yabuta N, Okada N, Ito A, Hosomi T, et al. Lats2 is an essential mitotic regulator required for the coordination of cell division. J Biol Chem. 2007;282:19259–71.

    Article  PubMed  CAS  Google Scholar 

  140. Lee KH, Goan YG, Hsiao M, et al. MicroRNA-373 (miR-373) post-transcriptionally regulates large tumor suppressor, homolog 2 (LATS2) and stimulates proliferation in human esophageal cancer. Exp Cell Res. 2009;315:2529–38.

    Article  PubMed  CAS  Google Scholar 

  141. Crosby ME, Kulshreshtha R, Ivan M, Glazer PM. MicroRNA regulation of DNA repair gene expression in hypoxic stress. Cancer Res. 2009;69:1221–9.

    Article  PubMed  CAS  Google Scholar 

  142. Hui AB, Lenarduzzi M, Krushel T, et al. Comprehensive MicroRNA profiling for head and neck squamous cell carcinomas. Clin Cancer Res. 2010;16:1129–39.

    Article  PubMed  CAS  Google Scholar 

  143. Xie Q, Chen X, Lu F, Zhang T, et al. Aberrant expression of microRNA 155 may accelerate cell proliferation by targeting sex-determining region Y box 6 in hepatocellular carcinoma. Cancer. 2012;118:2431–42.

    Google Scholar 

  144. Du ZM, Hu LF, Wang HY, et al. Upregulation of MiR-155 in nasopharyngeal carcinoma is partly driven by LMP1 and LMP2A and downregulates a negative prognostic marker JMJD1A. PLoS One. 2011;6:e19137.

    Article  PubMed  CAS  Google Scholar 

  145. Eis PS, Tam W, Sun L, et al. Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci USA. 2005;102:3627–32.

    Article  PubMed  CAS  Google Scholar 

  146. Nikiforova MN, Tseng GC, Steward D, Diorio D, Nikiforov YE. MicroRNA expression profiling of thyroid tumors: biological significance and diagnostic utility. J Clin Endocrinol Metab. 2008;93:1600–8.

    Article  PubMed  CAS  Google Scholar 

  147. Chen J, Wang BC, Tang JH. Clinical significance of MicoRNA-155 expression in human breast cancer. J Surg Oncol. 2011.

  148. Shibuya H, Iinuma H, Shimada R, Horiuchi A, Watanabe T. Clinicopathological and prognostic value of microRNA-21 and microRNA-155 in colorectal cancer. Oncology. 2010;79:313–20.

    Article  PubMed  CAS  Google Scholar 

  149. Wang X, Tang S, Le SY, et al. Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth. PLoS One. 2008;3:e2557.

    Article  PubMed  CAS  Google Scholar 

  150. Greither T, Grochola LF, Udelnow A, Lautenschläger C, Würl P, Taubert H. Elevated expression of microRNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival. Int J Cancer. 2010;126:73–80.

    Article  PubMed  CAS  Google Scholar 

  151. Yanaihara N, Caplen N, Bowman E, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006;9:189–98.

    Article  PubMed  CAS  Google Scholar 

  152. Philippidou D, Schmitt M, Moser D, Margue C, Nazarov PV, Muller A, Vallar L, Nashan D, Behrmann I, Kreis S. Signatures of microRNAs and selected microRNA target genes in human melanoma. Cancer Res. 2010;70:4163–73.

    Article  PubMed  CAS  Google Scholar 

  153. White NM, Bao TT, Grigull J, et al. miRNA profiling for clear cell renal cell carcinoma: biomarker discovery and identification of potential controls and consequences of miRNA dysregulation. J Urol. 2011;186:1077–83.

    Article  PubMed  CAS  Google Scholar 

  154. Rahadiani N, Takakuwa T, Tresnasari K, Morii E, Aozasa K. Latent membrane protein-1 of Epstein-Barr virus induces the expression of B-cell integration cluster, a precursor form of microRNA-155, in B lymphoma cell lines. Biochem Biophys Res Commun. 2008;377:579–83.

    Article  PubMed  CAS  Google Scholar 

  155. Gatto G, Rossi A, Rossi D, Kroening S, Bonatti S, Mallardo M. Epstein-Barr virus latent membrane protein 1 trans-activates miR-155 transcription through the NF-kappaB pathway. Nucleic Acids Res. 2008;36:6608–19.

    Article  PubMed  CAS  Google Scholar 

  156. Thompson RC, Herscovitch M, Zhao I, Ford TJ, Gilmore TD. NF-kappaB down-regulates expression of the B-lymphoma marker CD10 through a miR-155/PU.1 pathway. J Biol Chem. 2011;286:1675–82.

    Article  PubMed  CAS  Google Scholar 

  157. Moreau-Gachelin F. Spi-1/PU.1: an oncogene of the Ets family. Biochim Biophys Acta. 1994;1198:149–63.

    PubMed  Google Scholar 

  158. Jiang S, Zhang HW, Lu MH, et al. MicroRNA-155 functions as an OncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene. Cancer Res. 2010;70:3119–27.

    Article  PubMed  CAS  Google Scholar 

  159. Tili E, Michaille JJ, Wernicke D, Alder H, Costinean S, Volinia S, Croce CM. Mutator activity induced by microRNA-155 (miR-155) links inflammation and cancer. Proc Natl Acad Sci USA. 2011;108:4908–13.

    Article  PubMed  CAS  Google Scholar 

  160. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.

    Article  PubMed  CAS  Google Scholar 

  161. Zen K, Zhang CY. Circulating MicroRNAs: a novel class of biomarkers to diagnose and monitor human cancers. Med Res Rev. 2010.

  162. Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, Harano T, Yatabe Y, Nagino M, Nimura Y, Mitsudomi T, Takahashi T. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 2004;64:3753–6.

    Article  PubMed  CAS  Google Scholar 

  163. Lawrie CH, Gal S, Dunlop HM, et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol. 2008;141:672–5.

    Article  PubMed  Google Scholar 

  164. Gao W, Liu L, Lu X, Shu Y. Circulating microRNAs: possible prediction biomarkers for personalized therapy of non-small-cell lung carcinoma. Clin Lung Cancer. 2011;12:14–7.

    Article  PubMed  CAS  Google Scholar 

  165. Roos PH, Jakubowski N. Methods for the discovery of low-abundance biomarkers for urinary bladder cancer in biological fluids. Bioanalysis. 2010;2:295–309.

    Article  PubMed  CAS  Google Scholar 

  166. Mahn R, Heukamp LC, Rogenhofer S, von Ruecker A, Müller SC, Ellinger J. Circulating microRNAs (miRNA) in serum of patients with prostate cancer. Urology. 2011;77:1265.e9–16.

    Google Scholar 

  167. Wu WK, Lee CW, Cho CH, et al. MicroRNA dysregulation in gastric cancer: a new player enters the game. Oncogene. 2010;29:5761–71.

    Article  PubMed  CAS  Google Scholar 

  168. Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 2008;105:10513–8.

    Article  PubMed  CAS  Google Scholar 

  169. Ciesla M, Skrzypek K, Kozakowska M, Loboda A, Jozkowicz A, Dulak J. MicroRNAs as biomarkers of disease onset. Anal Bioanal Chem. 2011;401:2051–61.

    Article  PubMed  CAS  Google Scholar 

  170. Camussi G, Deregibus MC, Bruno S, Cantaluppi V, Biancone L. Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int. 2010;78:838–48.

    Article  PubMed  CAS  Google Scholar 

  171. Turchinovich A, Weiz L, Langheinz A, Burwinkel B. Characterization of extracellular circulating microRNA. Nucleic Acids Res. 2011;39:7223–33.

    Article  PubMed  CAS  Google Scholar 

  172. Lodes MJ, Caraballo M, Suciu D, Munro S, Kumar A, Anderson B. Detection of cancer with serum miRNAs on an oligonucleotide microarray. PLoS One. 2009;4:e6229.

    Article  PubMed  CAS  Google Scholar 

  173. Chen X, Ba Y, Ma L, Cai X, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18:997–1006.

    Article  PubMed  CAS  Google Scholar 

  174. Cortez MA, Bueso-Ramos C, Ferdin J, Lopez-Berestein G, Sood AK, Calin GA. MicroRNAs in body fluids—the mix of hormones and biomarkers. Nat Rev Clin Oncol. 2011;8:467–77.

    Article  PubMed  CAS  Google Scholar 

  175. Nana-Sinkam SP, Croce CM. MicroRNAs as therapeutic targets in cancer. Transl Res. 2011;157:216–25.

    Article  PubMed  CAS  Google Scholar 

  176. Garzon R, Marcucci G, Croce CM. Targeting microRNAs in cancer: rationale, strategies and challenges. Nat Rev Drug Discov. 2010;9:775–89.

    Article  PubMed  CAS  Google Scholar 

  177. Ebert MS, Sharp PA. MicroRNA sponges: progress and possibilities. RNA. 2010;16:2043–50.

    Article  PubMed  CAS  Google Scholar 

  178. Sotillo E, Thomas-Tikhonenko A. Shielding the messenger (RNA): microRNA-based anticancer therapies. Pharmacol Ther. 2011;131(1):18–32.

    Article  PubMed  CAS  Google Scholar 

  179. Montgomery RL, Hullinger TG, Semus HM, Dickinson BA, Seto AG, Lynch JM, Stack C, Latimer PA, Olson EN, van Rooij E. Therapeutic inhibition of miR-208a improves cardiac function and survival during heart failure. Circulation. 2011;124:1537–47.

    Article  PubMed  CAS  Google Scholar 

  180. Ma L, Young J, Prabhala H, Pan E, et al. miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol. 2010;12:247–56.

    PubMed  CAS  Google Scholar 

  181. Valastyan S, Reinhardt F, Benaich N, et al. A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell. 2009;137:1032–46.

    Article  PubMed  CAS  Google Scholar 

  182. Burchard J, Jackson AL, Malkov V, Needham RH, Tan Y, Bartz SR, Dai H, Sachs AB, Linsley PS. MicroRNA-like off-target transcript regulation by siRNAs is species specific. RNA. 2009;15:308–15.

    Article  PubMed  CAS  Google Scholar 

  183. Linsley PS, Jackson AL. Hidden reach of the micromanagers. BMC Biol. 2010;8:53.

    Article  PubMed  CAS  Google Scholar 

  184. Tirabassi R, Hook L, Landais I, Grey F, Meyers H, Hewitt H, Nelson J. Human cytomegalovirus US7 is regulated synergistically by two virally encoded microRNAs and by two distinct mechanisms. J Virol. 2011;85:11938–44.

    Article  PubMed  CAS  Google Scholar 

  185. Minakuchi Y, Takeshita F, Kosaka N, et al. Atelocollagen-mediated synthetic small interfering RNA delivery for effective gene silencing in vitro and in vivo. Nucleic Acids Res. 2004;32:e109.

    Article  PubMed  Google Scholar 

  186. Tazawa H, Tsuchiya N, Izumiya M, Nakagama H. Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells. Proc Natl Acad Sci USA. 2007;104:15472–7.

    Article  PubMed  CAS  Google Scholar 

  187. Wu Y, Crawford M, Yu B, Mao Y, Nana-Sinkam SP, Lee LJ. MicroRNA delivery by cationic lipoplexes for lung cancer therapy. Mol Pharm. 2011;8:1381–9.

    Article  PubMed  CAS  Google Scholar 

  188. Chen Y, Zhu X, Zhang X, Liu B, Huang L. Nanoparticles modified with tumor-targeting scFv deliver siRNA and miRNA for cancer therapy. Mol Ther. 2010;18:1650–6.

    Article  PubMed  CAS  Google Scholar 

  189. Pan J, Hu H, Zhou Z, et al. Tumor-suppressive mir-663 gene induces mitotic catastrophe growth arrest in human gastric cancer cells. Oncol Rep. 2010;24:105–12.

    PubMed  CAS  Google Scholar 

  190. Tan Gana NH, Victoriano AF, Okamoto T. Evaluation of online miRNA resources for biomedical applications. Genes Cells. 2012;17:11–27.

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8670, Japan

    Isamu Hoshino & Hisahiro Matsubara

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Hoshino, I., Matsubara, H. MicroRNAs in cancer diagnosis and therapy: from bench to bedside. Surg Today 43, 467–478 (2013). https://doi.org/10.1007/s00595-012-0392-5

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