Histone Modifications: The Double Edged Sword in Gynaecological Cancers
Abstract
Gynaecological cancers are one among the fatal cancers that affects women worldwide. It includes endometrial, ovarian, cervical, vaginal and vulvar cancers. Epigenetic aberrations play a crucial role in the development and progression of such cancers, which includes global genomic hypomethylation, Cytosine-Guanine (CpG) island promoter hypermethylation, changes in histone modifications and changes in chromatin-modifying enzymes. This review aims at elaborating the significance of epigenetic changes specifically the histone modifications, at H3K9, H3K27, H3K4 and others involved in gynaecological tumourigenesis. They can independently or synergistically act along with DNA methylation for repression of the tumour suppressor genes and possibly for the activation of various oncogenes like CLDN3, CLDN4, GATA4, etc. in gynaecological cancers. These modifications may pave the way in the future for the identification of biomarkers in early diagnosis and prognosis with an opportunity for targeted drug delivery. A systematic review was done using Internet based scientific databases. Relevant clues about the role of Histone modifications like acetylation, deacetylation, mono/di/trimethylation, demethylation of the histone tails (H3/H4) involved in tumour development and progression were reviewed.
Keywords:
Gynaecological Cancer, Histone modification, Acetylation, Deacetylation, Methylation, Demethylation
Downloads
Download data is not yet available.
References
1. CancerIndex. Gynaecological Cancers. Available at: http://www.cancerindex.org/clinks3g.htm
2. Centers for Disease Control and Prevention. Gynecologic Cancer Incidence, United States—2012–2016. Atlanta, GA: Centers for Disease Control and Prevention, US Department of Health and Human Services, USCS Data Brief, no 11. 2019.
3. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014; 64(1):9-29.
4. American Cancer Society(ACS). Treatment choices for Endometrial Cancer, by Stage. Available at: https://www.cancer.org/cancer/endometrial-cancer/treating/by-stage.html
5. Waddington CH. The epigenotype 1942. Int J Epidemiol. 2012;41(1):10-13.
6. Shikhar Sharma, Theresa K. Kelly, Peter A. Jones. Epigenetics in cancer. Carcinogenesis. 2010; 31(1): 27–36.
7. Feinberg AP, Ohlsson R, Henikoff S.The epigenetic progenitor origin of human cancer. Nat. Rev. Genet. 2006;7(1)21–33.
8. Wang Y, Leung FC. An evaluation of new criteria for CpG islands in the human genome as gene markers. Bioinformatics. 2004; 20(7):1170-1177
9. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002; 16(1):6-21.
10. Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU, Landsberger N, et al. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet. 1998; 19(2):187-191.
11. Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN, et al. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature.1998;393(6683):386-9.
12. Cutter AR1, Hayes JJ2.A brief review of nucleosome structure. FEBS Lett.2015; 589(20 Pt A):2914-2292
13. Kouzarides T. Chromatin modifications and their function. Cell. 2007; 128(4):693-705.
14. Feinberg AP, Vogelstein B. Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature. 1983;301(5895):89-92.
15. Hebbes TR, Thorne AW, Crane-Robinson. A direct link between core histone acetylation and transcriptionally active chromatin. C EMBO J. 1988 May; 7(5):1395-402.
16. Liang G, Lin JC, Wei V, Yoo C, Cheng JC, Nguyen CT, et al. Distinct localization of histone H3 acetylation and H3-K4 methylation to the transcription start sites in the human genome. Proc Natl Acad Sci USA. 2004;101(19):7357-7362.
17. Fardi M, Solali S, Farshdousti Hagh M. Epigenetic mechanisms as a new approach in cancer treatment: An updated review. Genes Dis. 2018; 5(4):304-311.
18. Haberland M, Montgomery RL, Olson EN. The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat. Rev. Genet. 2009; 10(1):32-42.
19. Sova P1, Feng Q, Geiss G, Wood T, Strauss R, Rudolf V, et al. Discovery of Novel Methylation Biomarkers in Cervical Carcinoma by Global Demethylation and Microarray Analysis, Cancer Epidemiol Biomarkers Prev. 2006; 15(1):114-23.
20. Alka Singh, Sameera Gupta, Manisha Sachan. Epigenetic Biomarkers in the Management of Ovarian Cancer: Current Prospectives. Frontiers in Cell and Developmental Biology. 2019;7:182.
21. Barnholtz-Sloan JS, Schwartz AG, Qureshi F, Jacques S, Malone J and Munkarah AR. Ovarian cancer: changes in patterns at diagnosis and relative survival over the last three decades. Am J Obstet Gynecol. 2003; 189(4):1120-1127.
22. Agarwal R, D'Souza T, Morin PJ. Claudin-3 and claudin-4 expression in ovarian epithelial cells enhances invasion and is associated with increased matrix metalloproteinase-2 activity. Cancer Res. 2005; 65(16):7378-85.
23. Litkouhi B, Kwong J, Lo CM, Smedley JG, McClane BA, Aponte M, et al. Claudin-4 overexpression in epithelial ovarian cancer is associated with hypomethylation and is a potential target for modulation of tight junction barrier function using a C-terminal fragment of Clostridium perfringens enterotoxin. Neoplasia. 2007; 9(4):304-314.
24. Honda H, Pazin MJ, Ji H, Wernyj RP, Morin PJ. Crucial roles of Sp1 and epigenetic modifications in the regulation of the CLDN4 promoter in ovarian cancer cells. J. Biol. Chem. 2006; 281(30): 21433–21444.
25. Honda H, Pazin MJ, D'Souza T, Ji H, Morin PJ. Regulation of the CLDN3 Gene in Ovarian Cancer Cells. Cancer Biol. Ther.2007; 6(11):1733-1742.
26. Mi Jeong Kwon, Sung-Su Kim, Yoon-La Choi, Hun Soon Jung, Curt Balch, Su-Hyeong Kim, et al. Derepression of CLDN3 and CLDN4 during ovarian tumorigenesis is associated with loss of repressive histone modifications. Carcinogenesis. 2010; 31(6): 974–983.
27. Bai Y, Akiyama Y, Nagasaki H, Yagi OK, Kikuchi Y, Saito N, et al. Distinct expression of CDX2 and GATA4/5, development-related genes, in human gastric cancer cell lines. Mol Carcinog. 2000; 28(3):184-188.
28. Mok SC, Chan WY, Wong KK, Cheung KK, Lau CC, SW Ng, et al. DOC-2 A candidate tumour suppressor gene in human epithelial ovarian cancer. Oncogene. 1998; 16: 2381–2387.
29. Caslini C, Capo-chichi C, Roland IH, Nicolas E, Yeung AT, Xu XX. Histone modifications silence the GATA transcription factor genes in ovarian cancer. Oncogene. 2006; 25(39):5446-5461.
30. Meng CF, Su B, Li W. DNA demethylation is superior to histone acetylation for reactivating cancer-associated genes in ovarian cancer cells. Molecular Medicine Reports. 2011; 4(6):1273-1278.
31. Mark A Brown, Robert J Sims, Paul D Gottlieb and Philip W Tucker. Identification and characterization of Smyd2: a split SET/MYND domain-containing histone H3 lysine 36-specific methyltransferase that interacts with the Sin3 histone deacetylase complex. Mol. Cancer. 2006; 5: 26.
32. Kukita A, Sone K, Oda K, Hamamoto R, Kaneko S, Komatsu M, et al. Histone methyltransferase SMYD2 selective inhibitor LLY-507 in combination with poly ADP ribose polymerase inhibitor has therapeutic potential against high-grade serous ovarian carcinomas. Biochemical and Biophysical Research Communications. 2019; 513(2):340-346.
33. Zhao H, Dupont J, Yakar S, Karas M, LeRoith D. PTEN inhibits cell proliferation and induces apoptosis by downregulating cell surface IGF-IR expression in prostate cancer cells. Oncogene. 2004; 23(3):786-794.
34. Sigurd F. Lax. Pathology of Endometrial Carcinoma. Springer International Publishing AG. 2017; 943:75-96.
35. National Cancer Institute (NIH). Cancer Stat Facts: Endometrial Cancer. Available at: https://seer.cancer.gov/statfacts/html/corp.html Accessed November27, 2017
36. Qing Li, Nan Jia, Xiang Tao, Keqin Hua , Weiwei Feng. The expression and significance of histone lysine methylation in endometrial cancer. Oncology Letters. 2017; 14(5): 6210–6216.
37. Soussi T: Role of the p53 gene in human malignant tumors. A major discovery in oncology. Rev Prat. 1999; 43(19):2531-5. (In French).
38. Mellor J. Dynamic nucleosomes and gene transcription. Trends Genet. 2006; 22(6):320-329.
39. Yuji Ohno, Hattori A, Yoshiki T, Kakeya H. Association of epigenetic alterations in the human C7orf24 gene with the aberrant gene expression in malignant cells. J. Biochem. 2013;154(4):355–362.
40. Sitruk-Ware R, Plu-Bureau G. Progestins and cancer. Gynecol endocrinol 13. 1999;23(4):290-6.
41. Markman M. Hormonal therapy of endometrial cancer. Eur J Cancer. 2005; 41(5):673-675.
42. Dai D, Wolf DM, Litman ES, White MJ, Leslie KK. Progesterone inhibits human endometrial cancer cell growth and invasiveness: down-regulation of cellular adhesion molecules through progesterone B receptors. Cancer Res. 2002; 62(3):881-886.
43. Chu Y, Wang Y, Zhang G, Chen H, Dowdy SC, Xiong Y, et al. Chromatin composition alterations and the critical role of MeCP2 for epigenetic silencing of progesterone receptor B gene in endometrial cancers. Cell. Mol. Life Sci.2014; 71(17):3393-3408.
44. World Health Organisation(WHO). Cancer Early Diagnosis and Screening Cervical Cancer. Available at: https://www.who.int/cancer/prevention/diagnosis-screening/cervical-cancer/en/
45. J.M. Walboomers, M.V. Jacobs, M.M. Manos, F.X. Bosch, J.A. Kummer, K.V. Shah, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J. Pathol. 1999; 189 (1) 12–19.
46. Y.T. Wang, J.Y. Chuang, M.R. Shen, W.B. Yang, W.C. Chang, J.J. Hung. Sumoylation of specificity protein 1 augments its degradation by changing the localization and increasing the specificity protein 1 proteolytic process. J. Mol. Biol. 2008; 380 (5): 869–885.
47. Lin WC, Yan MD, Yu PN, Li HJ, Kuo CC, Hsu CL, et al. The role of Sp1 and EZH2 in the regulation of LMX1A in cervical cancer cells. Biochimica et BiophysicaActa. 2013; 1833(12): 3206–3217.
48. Nervi C, De Marinis E, Codacci-Pisanelli G. Epigenetic treatment of solid tumours: a review of clinical trials. Clinical Epigenetics. 2015; 7:127.
2. Centers for Disease Control and Prevention. Gynecologic Cancer Incidence, United States—2012–2016. Atlanta, GA: Centers for Disease Control and Prevention, US Department of Health and Human Services, USCS Data Brief, no 11. 2019.
3. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014; 64(1):9-29.
4. American Cancer Society(ACS). Treatment choices for Endometrial Cancer, by Stage. Available at: https://www.cancer.org/cancer/endometrial-cancer/treating/by-stage.html
5. Waddington CH. The epigenotype 1942. Int J Epidemiol. 2012;41(1):10-13.
6. Shikhar Sharma, Theresa K. Kelly, Peter A. Jones. Epigenetics in cancer. Carcinogenesis. 2010; 31(1): 27–36.
7. Feinberg AP, Ohlsson R, Henikoff S.The epigenetic progenitor origin of human cancer. Nat. Rev. Genet. 2006;7(1)21–33.
8. Wang Y, Leung FC. An evaluation of new criteria for CpG islands in the human genome as gene markers. Bioinformatics. 2004; 20(7):1170-1177
9. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002; 16(1):6-21.
10. Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU, Landsberger N, et al. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet. 1998; 19(2):187-191.
11. Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN, et al. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature.1998;393(6683):386-9.
12. Cutter AR1, Hayes JJ2.A brief review of nucleosome structure. FEBS Lett.2015; 589(20 Pt A):2914-2292
13. Kouzarides T. Chromatin modifications and their function. Cell. 2007; 128(4):693-705.
14. Feinberg AP, Vogelstein B. Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature. 1983;301(5895):89-92.
15. Hebbes TR, Thorne AW, Crane-Robinson. A direct link between core histone acetylation and transcriptionally active chromatin. C EMBO J. 1988 May; 7(5):1395-402.
16. Liang G, Lin JC, Wei V, Yoo C, Cheng JC, Nguyen CT, et al. Distinct localization of histone H3 acetylation and H3-K4 methylation to the transcription start sites in the human genome. Proc Natl Acad Sci USA. 2004;101(19):7357-7362.
17. Fardi M, Solali S, Farshdousti Hagh M. Epigenetic mechanisms as a new approach in cancer treatment: An updated review. Genes Dis. 2018; 5(4):304-311.
18. Haberland M, Montgomery RL, Olson EN. The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat. Rev. Genet. 2009; 10(1):32-42.
19. Sova P1, Feng Q, Geiss G, Wood T, Strauss R, Rudolf V, et al. Discovery of Novel Methylation Biomarkers in Cervical Carcinoma by Global Demethylation and Microarray Analysis, Cancer Epidemiol Biomarkers Prev. 2006; 15(1):114-23.
20. Alka Singh, Sameera Gupta, Manisha Sachan. Epigenetic Biomarkers in the Management of Ovarian Cancer: Current Prospectives. Frontiers in Cell and Developmental Biology. 2019;7:182.
21. Barnholtz-Sloan JS, Schwartz AG, Qureshi F, Jacques S, Malone J and Munkarah AR. Ovarian cancer: changes in patterns at diagnosis and relative survival over the last three decades. Am J Obstet Gynecol. 2003; 189(4):1120-1127.
22. Agarwal R, D'Souza T, Morin PJ. Claudin-3 and claudin-4 expression in ovarian epithelial cells enhances invasion and is associated with increased matrix metalloproteinase-2 activity. Cancer Res. 2005; 65(16):7378-85.
23. Litkouhi B, Kwong J, Lo CM, Smedley JG, McClane BA, Aponte M, et al. Claudin-4 overexpression in epithelial ovarian cancer is associated with hypomethylation and is a potential target for modulation of tight junction barrier function using a C-terminal fragment of Clostridium perfringens enterotoxin. Neoplasia. 2007; 9(4):304-314.
24. Honda H, Pazin MJ, Ji H, Wernyj RP, Morin PJ. Crucial roles of Sp1 and epigenetic modifications in the regulation of the CLDN4 promoter in ovarian cancer cells. J. Biol. Chem. 2006; 281(30): 21433–21444.
25. Honda H, Pazin MJ, D'Souza T, Ji H, Morin PJ. Regulation of the CLDN3 Gene in Ovarian Cancer Cells. Cancer Biol. Ther.2007; 6(11):1733-1742.
26. Mi Jeong Kwon, Sung-Su Kim, Yoon-La Choi, Hun Soon Jung, Curt Balch, Su-Hyeong Kim, et al. Derepression of CLDN3 and CLDN4 during ovarian tumorigenesis is associated with loss of repressive histone modifications. Carcinogenesis. 2010; 31(6): 974–983.
27. Bai Y, Akiyama Y, Nagasaki H, Yagi OK, Kikuchi Y, Saito N, et al. Distinct expression of CDX2 and GATA4/5, development-related genes, in human gastric cancer cell lines. Mol Carcinog. 2000; 28(3):184-188.
28. Mok SC, Chan WY, Wong KK, Cheung KK, Lau CC, SW Ng, et al. DOC-2 A candidate tumour suppressor gene in human epithelial ovarian cancer. Oncogene. 1998; 16: 2381–2387.
29. Caslini C, Capo-chichi C, Roland IH, Nicolas E, Yeung AT, Xu XX. Histone modifications silence the GATA transcription factor genes in ovarian cancer. Oncogene. 2006; 25(39):5446-5461.
30. Meng CF, Su B, Li W. DNA demethylation is superior to histone acetylation for reactivating cancer-associated genes in ovarian cancer cells. Molecular Medicine Reports. 2011; 4(6):1273-1278.
31. Mark A Brown, Robert J Sims, Paul D Gottlieb and Philip W Tucker. Identification and characterization of Smyd2: a split SET/MYND domain-containing histone H3 lysine 36-specific methyltransferase that interacts with the Sin3 histone deacetylase complex. Mol. Cancer. 2006; 5: 26.
32. Kukita A, Sone K, Oda K, Hamamoto R, Kaneko S, Komatsu M, et al. Histone methyltransferase SMYD2 selective inhibitor LLY-507 in combination with poly ADP ribose polymerase inhibitor has therapeutic potential against high-grade serous ovarian carcinomas. Biochemical and Biophysical Research Communications. 2019; 513(2):340-346.
33. Zhao H, Dupont J, Yakar S, Karas M, LeRoith D. PTEN inhibits cell proliferation and induces apoptosis by downregulating cell surface IGF-IR expression in prostate cancer cells. Oncogene. 2004; 23(3):786-794.
34. Sigurd F. Lax. Pathology of Endometrial Carcinoma. Springer International Publishing AG. 2017; 943:75-96.
35. National Cancer Institute (NIH). Cancer Stat Facts: Endometrial Cancer. Available at: https://seer.cancer.gov/statfacts/html/corp.html Accessed November27, 2017
36. Qing Li, Nan Jia, Xiang Tao, Keqin Hua , Weiwei Feng. The expression and significance of histone lysine methylation in endometrial cancer. Oncology Letters. 2017; 14(5): 6210–6216.
37. Soussi T: Role of the p53 gene in human malignant tumors. A major discovery in oncology. Rev Prat. 1999; 43(19):2531-5. (In French).
38. Mellor J. Dynamic nucleosomes and gene transcription. Trends Genet. 2006; 22(6):320-329.
39. Yuji Ohno, Hattori A, Yoshiki T, Kakeya H. Association of epigenetic alterations in the human C7orf24 gene with the aberrant gene expression in malignant cells. J. Biochem. 2013;154(4):355–362.
40. Sitruk-Ware R, Plu-Bureau G. Progestins and cancer. Gynecol endocrinol 13. 1999;23(4):290-6.
41. Markman M. Hormonal therapy of endometrial cancer. Eur J Cancer. 2005; 41(5):673-675.
42. Dai D, Wolf DM, Litman ES, White MJ, Leslie KK. Progesterone inhibits human endometrial cancer cell growth and invasiveness: down-regulation of cellular adhesion molecules through progesterone B receptors. Cancer Res. 2002; 62(3):881-886.
43. Chu Y, Wang Y, Zhang G, Chen H, Dowdy SC, Xiong Y, et al. Chromatin composition alterations and the critical role of MeCP2 for epigenetic silencing of progesterone receptor B gene in endometrial cancers. Cell. Mol. Life Sci.2014; 71(17):3393-3408.
44. World Health Organisation(WHO). Cancer Early Diagnosis and Screening Cervical Cancer. Available at: https://www.who.int/cancer/prevention/diagnosis-screening/cervical-cancer/en/
45. J.M. Walboomers, M.V. Jacobs, M.M. Manos, F.X. Bosch, J.A. Kummer, K.V. Shah, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J. Pathol. 1999; 189 (1) 12–19.
46. Y.T. Wang, J.Y. Chuang, M.R. Shen, W.B. Yang, W.C. Chang, J.J. Hung. Sumoylation of specificity protein 1 augments its degradation by changing the localization and increasing the specificity protein 1 proteolytic process. J. Mol. Biol. 2008; 380 (5): 869–885.
47. Lin WC, Yan MD, Yu PN, Li HJ, Kuo CC, Hsu CL, et al. The role of Sp1 and EZH2 in the regulation of LMX1A in cervical cancer cells. Biochimica et BiophysicaActa. 2013; 1833(12): 3206–3217.
48. Nervi C, De Marinis E, Codacci-Pisanelli G. Epigenetic treatment of solid tumours: a review of clinical trials. Clinical Epigenetics. 2015; 7:127.
Published
01-05-2020
Statistics
330 Views | 273 Downloads
Citatons
How to Cite
1.
M JJ, Mishra B. Histone Modifications: The Double Edged Sword in Gynaecological Cancers. World Journal of Current Med and Pharm Research [Internet]. 2020May1 [cited 2024Dec.6];2(2):120-4. Available from: https://wjcmpr.com/index.php/journal/article/view/112
Section
Review Articles
Copyright © Author(s) retain the copyright of this article.
