Document Type : Review Article

Authors

1 Assistant Professor, Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

2 Assistant Professor, Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

3 Professor, Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

Abstract

Cancer is caused by aberrant genetic and epigenetic changes in genes expression. DNA methylation, histone modification, and microRNAs gene deregulation are the most known epigenetic changes in different stages of cancer. Since every tumor has its own specific epigenome, any abnormal pattern is a potential biomarker for classification of different types of tumors. Despite, tumorigenesis, abnormal epigenetic changes are highly correlated with drug resistance in various stages of cancer. But, reversible nature of these abnormalities is the basis of epigenetic cancer treatment. Drugs affecting the epigenome are the new hopes in cancer treatment. The aim of this study was to investigate the role of epigenetics in tumorigenesis and also drug resistance in cancers.

Keywords

  1. Berger SL, Kouzarides T, Shiekhattar R, Shilatifard A. An operational definition of epigenetics. Genes Dev 2009; 23(7):781-3.
  2. Badia E, Oliva J, Balaguer P, Cavaillès V. Tamoxifen resistance and epigenetic modifications in breast cancer cell lines. Curr Med Chem 2007; 14(28):3035-45.
  3. Gottesman MM. Mechanisms of cancer drug resistance Annu Rev Med 2002; 53:615-27.
  4. Babashah S, Soleimani M. The oncogenic and tumour suppressive roles of microRNAs in cancer and apoptosis. Eur J Cancer 2011; 47(8):1127-37.
  5. Mathers JC. Nutritional modulation of ageing: genomic and epigenetic approaches. Mech Ageing Dev 2006; 127(6):584-9.
  6. Ghasemi S, Mozdarani H, Soleimani M. The Effect of miR-372 on Genome Instability in MKN-45 Cell Line. J Isfahan Med Sch 2015; 32(311): 2035-47. Persian
  7. Daniel M, Peek GW, Tollefsbol TO. Regulation of the human catalytic subunit of telomerase (hTERT). Gene 2012; 498(2):135-46.
  8. Kouzarides T. Chromatin modifications and their function. Cell 2007; 128(4):693-705.
  9. Wang J, Zhang KY, Liu SM, Sen S. Tumor-associated circulating microRNAs as biomarkers of cancer. Molecules 2014; 19(2):1912-38.
  10. Housman G, Byler S, Heerboth S, Lapinska K, Longacre M, Snyder N, et al. Drug resistance in cancer: an overview. Cancers (Basel) 2014; 6(3):1769-92.
  11. Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG. Cancer drug resistance: an evolving paradigm. Nat Rev Cancer 2013; 13(10):714-26.
  12. Shoemaker RH. Genetic and epigenetic factors in anticancer drug resistance. J Natl Cancer Inst 2000; 92(1):4-5.
  13. Byler S, Sarkar S. Do epigenetic drug treatments hold the key to killing cancer progenitor cells?  Epigenomics 2014; 6(2):161-5.
  14. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest 2009; 119(6): 1420–28.
  15. Zahreddine H, Borden KL. Mechanisms and insights into drug resistance in cancer. Front Pharmacol 2013; 4:28.
  16. Stavrovskaya AA. Cellular mechanisms of multidrug resistance of tumor cells. Biochemistry (Mosc) 2000; 65(1):95-106.
  17. Chang G, Roth C. Structure of MsbA from E. coli: a homolog of the multidrug resistance ATP binding cassette (ABC) transporters. Science 2001; 293(5536):1793-800.
  18. Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer 2002; 2(1):48-58.
  19. Kantharidis P, El-Osta A, deSilva M, Wall DM, Hu XF, Slater A, et al. Altered methylation of the human MDR1 promoter is associated with acquired multidrug resistance. Clin Cancer Res 1997; 3(11):2025-32.
  20. Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci U S A 1999; 96(15):8681-6.
  21. Hughes LA, Khalid-de Bakker CA, Smits KM, van den Brandt PA, Jonkers D, Ahuja N, et al. The CpG island methylator phenotype in colorectal cancer: progress and problems. Biochim Biophys Acta 2012; 1825(1):77-85.
  22. Hughes LA, Melotte V, de Schrijver J, de Maat M, Smit VT, Bovée JV, et al. The CpG island methylator phenotype: what's in a name? Cancer Res 2013; 73(19):5858-68.
  23. Nazemalhosseini Mojarad E, Kuppen PJ, Aghdaei HA, Zali MR. The CpG island methylator phenotype (CIMP) in colorectal cancer. Gastroenterol Hepatol Bed Bench 2013; 6(3):120-8.
  24. Schernhammer ES, Giovannucci E, Baba Y, Fuchs CS, Ogino S. B vitamins, methionine and alcohol intake and risk of colon cancer in relation to BRAF mutation and CpG island methylator phenotype (CIMP). PLoS One. 2011; 6(6):e21102.
  25. Samowitz WS, Albertsen H, Sweeney C, Herrick J, Caan BJ, Anderson KE, et al. Association of smoking, CpG island methylator phenotype, and V600E BRAF mutations in colon cancer. J Natl Cancer Inst 2006; 98(23):1731-8.
  26. Turcan S, Rohle D, Goenka A, Walsh LA, Fang F, Yilmaz E, et al. IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature 2012; 483(7390):479-83.
  27. Issa JP. Colon cancer: it's CIN or CIMP. Clin Cancer Res 2008; 14(19):5939-40.
  28. Zhang QY, Yi DQ, Zhou L, Zhang DH, Zhou TM. Status and significance of CpG island methylator phenotype in endometrial cancer. Gynecol Obstet Invest 2011; 72(3):183-91
  29. Singh A, Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene 2010; 29(34):4741-51.
  30. Zhou BB, Zhang H, Damelin M, Geles KG, Grindley JC, Dirks PB. Tumour-initiating cells: challenges and opportunities for anticancer drug discovery. Nat Rev Drug Discov 2009; 8(10):806-23.
  31. Muñoz P, Iliou MS, Esteller M. Epigenetic alterations involved in cancer stem cell reprogramming. Mol Oncol 2012; 6(6):620-36.
  32. Baccelli I, Trumpp A. The evolving concept of cancer and metastasis stem cells. J Cell Biol 2012; 198(3):281-93.
  33. Bonnet D1, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 1997; 3(7):730-7.
  34. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001; 414(6859):105-11.
  35. Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, et al. Cancer stem cells--perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res 2006; 66(19):9339-44.
  36. Li X, Pan YZ, Seigel GM, Hu ZH, Huang M, Yu AM. Breast cancer resistance protein BCRP/ABCG2 regulatory microRNAs (hsa-miR-328, -519c and -520h) and their differential expression in stem-like ABCG2+ cancer cells. Biochem Pharmacol 2011; 81(6):783-92.
  37. Crea F, Danesi R, Farrar WL. Cancer stem cell epigenetics and chemoresistance. Epigenomics 2009; 1(1):63-79.
  38. Aguilera O, Fernández AF, Muñoz A, Fraga MF. Epigenetics and environment: a complex relationship. J Appl Physiol (1985) 2010; 109(1):243-51.
  39. Daniel M, Tollefsbol TO. Epigenetic linkage of aging, cancer and nutrition. J Exp Biol. 2015; 218(Pt 1):59-70.
  40. Sharma S, Kelly TK, Jones PA. Epigenetics in cancer. Carcinogenesis. 2010; 31(1): 27–36.
  41. Feinberg AP, Tycko B. The history of cancer epigenetics. Nat Rev Cancer 2004; 4(2):143-53.
  42. Dawson MA, Kouzarides T. Cancer epigenetics: from mechanism to therapy. Cell 2012; 150(1):12-27.
  43. Glasspool RM, Teodoridis JM, Brown R. Epigenetics as a mechanism driving polygenic clinical drug resistance. Br J Cancer 2006; 94(8): 1087–92.
  44. Giacinti L, Claudio PP, Lopez M, Giordano A. Epigenetic information and estrogen receptor alpha expression in breast cancer. Oncologist. 2006; 11(1):1-8.
  45.  Choi SW, Friso S. Epigenetics: A New Bridge between Nutrition and Health. Adv Nutr 2010; 1(1): 8-16.
  46. Farshdousti Hagh M, Noruzinia M, Mortazavi Y, Soleimani M, Kaviani S, Mahmoodinia Maymand M. Epigenetic changes of RUNX2 and DLX5 genes in osteoblastic differentiation induced by zoledronic acid in mesenchymal stem cells. Modares Journal of Medical Sciences (Pathobiology) 2011; 14(1):59-69. Persian
  47. Yoo CB, Jones PA. Epigenetic therapy of cancer: past, present and future. Nat Rev Drug Discov 2006; 5(1):37-50.
  48. Johnson C, Warmoes MO, Shen X, Locasale JW. Epigenetics and cancer metabolism. Cancer Lett 2015; 356(2 Pt A):309-14.
  49. Olden K, Freudenberg N, Dowd J, Shields AE. Discovering how environmental exposures alter genes could lead to new treatments for chronic illnesses. Health Aff (Millwood) 2011; 30(5):833-41.
  50. Esteller M. CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter future. Oncogene 2002; 21(35):5427-40.
  51. Martinez-Cardús A, Martinez-Balibrea E, Bandrés E, Malumbres R, Ginés A, Manzano JL, et al. Pharmacogenomic approach for the identification of novel determinants of acquired resistance to oxaliplatin in colorectal cancer. Mol Cancer Ther 2009; 8(1):194-202.
  52. Tollefsbol TO. Dietary epigenetics in cancer and aging. Cancer Treat Res 2014; 159:257-67.
  53. Kristensen LS, Nielsen HM, Hansen LL. Epigenetics and cancer treatment. Eur J Pharmacol 2009; 625(1-3):131-42.
  54. Rodríguez-Paredes M, Esteller M. Cancer epigenetics reaches mainstream oncology. Nat Med 2011; 17(3):330-9.
  55. Balch C, Nephew KP. Epigenetic targeting therapies to overcome chemotherapy resistance. Adv Exp Med Biol 2013; 754:285-311.
  56. Krutovskikh VA, Herceg Z. Oncogenic microRNAs (OncomiRs) as a new class of cancer biomarkers. Bioessays. 2010; 32(10):894-904.
  57. Shukla S, Meeran SM.Epigenetics of cancer stem cells: Pathways and therapeutics. Biochim Biophys Acta 2014; 1840(12):3494-3502.