A Review of Aberrant DNA Methylation and Epigenetic Agents Targeting DNA Methyltransferases in Endometriosis

Author(s): Leilei Ding, Li Yang*, Chenchen Ren*, Huawen Zhang, Jie Lu, Senyan Wang, Zimeng Wu, Yanan Yang

Journal Name: Current Drug Targets

Volume 21 , Issue 11 , 2020


  Journal Home
Translate in Chinese
Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Background: Endometriosis (EMS) is a gynecological disease defined by the translocation and growth of endometrial tissue in other tissues or organs outside the uterus. Its clinical manifestations are dysmenorrhea, irregular menstruation, and even infertility. Although EMS is a benign disease, it has the characteristics of malignant tumor and the potential of malignant transformation. Recent studies have found that EMS may involve epigenetic changes and that various epigenetic aberrations, especially aberrant DNA methylation may play an essential role in the pathogenesis of EMS. Previous studies have elucidated the epigenetic regulators of EMS and reported variations in epigenetic patterns of genes known to be associated with abnormal hormonal, immune, and inflammatory states of EMS. With the development of high-throughput sequencing and other biomolecular technologies, we have a better understanding of genome-wide methylation in EMS.

Objective: This article will discuss the potentiality of targeting DNA methylation as the therapeutic approach for EMS.

Results: This article reviews the role of DNA methylation in the pathophysiology of EMS and provides insight into a novel therapeutic approach for EMS by targeting DNA methylation modifiers. We also review the current progress in using DNA methylation inhibitors in EMS therapy and the potential promise and challenges ahead.

Conclusion: Aberrant DNA methylation plays an essential role in the pathogenesis of EMS and epigenetic agents targeting DNA methyltransferases are expected to be the theoretical basis for the new treatment of EMS.

Keywords: Endometriosis, aberrant DNA methylation, gene, pathway, DNMTs, DNMTs inhibitors.

[1]
Guo SW. Genesis, genes and epigenetics of endometriosis-associated infertility. Nat Rev Endocrinol 2019; 15(5): 259-60.
[http://dx.doi.org/10.1038/s41574-019-0191-9] [PMID: 30886366]
[2]
Benagiano G, Brosens I, Lippi D. The history of endometriosis. Gynecol Obstet Invest 2014; 78(1): 1-9.
[http://dx.doi.org/10.1159/000358919] [PMID: 24853333]
[3]
Zondervan KT, Becker CM, Koga K, Missmer SA, Taylor RN, Viganò P. Endometriosis. Nat Rev Dis Primers 2018; 4(1): 9.
[http://dx.doi.org/10.1038/s41572-018-0008-5] [PMID: 30026507]
[4]
Giudice LC, Kao LC. Endometriosis. Lancet 2004; 364(9447): 1789-99.
[http://dx.doi.org/10.1016/S0140-6736(04)17403-5] [PMID: 15541453]
[5]
Taylor RN, Yu J, Torres PB, et al. Mechanistic and therapeutic implications of angiogenesis in endometriosis. Reprod Sci 2009; 16(2): 140-6.
[http://dx.doi.org/10.1177/1933719108324893] [PMID: 19001553]
[6]
Wells M. Recent advances in endometriosis with emphasis on pathogenesis, molecular pathology, and neoplastic transformation. Int J Gynecol Pathol 2004; 23(4): 316-20.
[http://dx.doi.org/10.1097/01.pgp.0000139636.94352.89] [PMID: 15381900]
[7]
Prowse AH, Manek S, Varma R, et al. Molecular genetic evidence that endometriosis is a precursor of ovarian cancer. Int J Cancer 2006; 119(3): 556-62.
[http://dx.doi.org/10.1002/ijc.21845] [PMID: 16506222]
[8]
Vigano P, Somigliana E, Chiodo I, Abbiati A, Vercellini P. Molecular mechanisms and biological plausibility underlying the malignant transformation of endometriosis: a critical analysis. Hum Reprod Update 2019; 12(1): 77-89.
[9]
Borghese B, Zondervan KT, Abrao MS, Chapron C, Vaiman D. Recent insights on the genetics and epigenetics of endometriosis. Clin Genet 2017; 91(2): 254-64.
[http://dx.doi.org/10.1111/cge.12897] [PMID: 27753067]
[10]
Koninckx PR, Ussia A, Adamyan L, Wattiez A, Gomel V, Martin DC. Pathogenesis of endometriosis: the genetic/epigenetic theory. Fertil Steril 2019; 111(2): 327-40.
[http://dx.doi.org/10.1016/j.fertnstert.2018.10.013] [PMID: 30527836]
[11]
Magzoub MM, Prunello M, Brennan K, Gevaert O. The impact of DNA methylation on the cancer proteome. PLOS Comput Biol 2019; 15(7): e1007245.
[http://dx.doi.org/10.1371/journal.pcbi.1007245] [PMID: 31356589]
[12]
Claus R, Lucas DM, Stilgenbauer S, et al. Quantitative DNA methylation analysis identifies a single CpG dinucleotide important for ZAP-70 expression and predictive of prognosis in chronic lymphocytic leukemia. J Clin Oncol 2012; 30(20): 2483-91.
[http://dx.doi.org/10.1200/JCO.2011.39.3090] [PMID: 22564988]
[13]
Kaiser MF, Johnson DC, Wu P, et al. Global methylation analysis identifies prognostically important epigenetically inactivated tumor suppressor genes in multiple myeloma. Blood 2013; 122(2): 219-26.
[http://dx.doi.org/10.1182/blood-2013-03-487884] [PMID: 23699600]
[14]
Koukoura O, Sifakis S, Spandidos DA. DNA methylation in endometriosis. (Review). Mol Med Rep 2016; 13(4): 2939-48.
[http://dx.doi.org/10.3892/mmr.2016.4925] [PMID: 26934855]
[15]
Kaei Nasu YK. Kentaro Kai, Yoko Aoyagi, Wakana Abe, Mamiko Okamoto, Hisashi Narahara. Aberrant histone modification in endometriosis. Front Biosci 2014; 1202-14.
[16]
Laudanski P, Mariusz Kuzmicki RC, Szamatowicz J, Charkiewicz A, Niklinski J. MicroRNAs expression profiling of eutopic proliferative endometrium in women with ovarian endometriosis. Reprod Biol Endocrinol 2013; 15(11): 78.
[17]
He J, Chang W, Feng C, Cui M, Xu T. Endometriosis Malignant Transformation: Epigenetics as a Probable Mechanism in Ovarian Tumorigenesis. Int J Genomics 2018.20181465348
[http://dx.doi.org/10.1155/2018/1465348] [PMID: 29780815]
[18]
James G, Herman MD, Stephen B. Baylin, M.D. Gene Silencing in Cancer in Association with Promoter Hypermethylation. N Engl J Med 2003; (349): 2042-54.
[19]
Lei H, Oh SP, Okano M, et al. De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells. Development 1996; 122(10): 3195-205.
[PMID: 8898232]
[20]
Xiong Y, Dowdy SC, Xue A, et al. Opposite alterations of DNA methyltransferase gene expression in endometrioid and serous endometrial cancers. Gynecol Oncol 2005; 96(3): 601-9.
[http://dx.doi.org/10.1016/j.ygyno.2004.11.047] [PMID: 15721400]
[21]
Sun L, Huang L, Nguyen P, et al. DNA methyltransferase 1 and 3B activate BAG-1 expression via recruitment of CTCFL/BORIS and modulation of promoter histone methylation. Cancer Res 2008; 68(8): 2726-35.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-6654] [PMID: 18413740]
[22]
Trowbridge JJ, Sinha AU, Zhu N, Li M, Armstrong SA, Orkin SH. Haploinsufficiency of Dnmt1 impairs leukemia stem cell function through derepression of bivalent chromatin domains. Genes Dev 2012; 26(4): 344-9.
[http://dx.doi.org/10.1101/gad.184341.111] [PMID: 22345515]
[23]
Wu Y, Strawn E, Basir Z, Halverson G, Guo SW. Aberrant expression of deoxyribonucleic acid methyltransferases DNMT1, DNMT3A, and DNMT3B in women with endometriosis. Fertil Steril 2007; 87(1): 24-32.
[http://dx.doi.org/10.1016/j.fertnstert.2006.05.077] [PMID: 17081533]
[24]
van Kaam KJ, Delvoux B, Romano A, D’Hooghe T, Dunselman GA, Groothuis PG. Deoxyribonucleic acid methyltransferases and methyl-CpG-binding domain proteins in human endometrium and endometriosis. Fertil Steril 2011; 95(4): 1421-7.
[http://dx.doi.org/10.1016/j.fertnstert.2011.01.031] [PMID: 21316665]
[25]
Saare M, Modhukur V, Suhorutshenko M, et al. The influence of menstrual cycle and endometriosis on endometrial methylome. Clin Epigenetics 2016; 8: 2.
[http://dx.doi.org/10.1186/s13148-015-0168-z] [PMID: 26759613]
[26]
Xinsheng Nan H-HN, Colin A. Johnson. Transcriptional repressionby themethyl-CpG-binding proteinMeCP2 involvesa histonedeacetylasecomplex. nature 1998.
[27]
Peter L. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. nature genetics 1998; 19
[28]
Wang L, Zhao J, Li Y, Wang Z, Kang S. Genome-wide analysis of DNA methylation in endometriosis using Illumina Human Methylation 450 K BeadChips. Mol Reprod Dev 2019; 86(5): 491-501.
[http://dx.doi.org/10.1002/mrd.23127] [PMID: 30740831]
[29]
Xue Q, Lin Z, Cheng YH, et al. Promoter methylation regulates estrogen receptor 2 in human endometrium and endometriosis. Biol Reprod 2007; 77(4): 681-7.
[http://dx.doi.org/10.1095/biolreprod.107.061804] [PMID: 17625110]
[30]
Xue Q, Lin Z, Yin P, Milad MP, Cheng YH, Confino E, et al. Transcriptional activation of steroidogenic factor-1 by hypomethylation of the 5′ CpG island in endometriosis. J Clin Endocrinol Metab 2007; 92(8): 3261-7.
[http://dx.doi.org/10.1210/jc.2007-0494] [PMID: 17519303]
[31]
Wu Y, Halverson G, Basir Z, Strawn E, Yan P, Guo SW. Aberrant methylation at HOXA10 may be responsible for its aberrant expression in the endometrium of patients with endometriosis. Am J Obstet Gynecol 2005; 193(2): 371-80.
[http://dx.doi.org/10.1016/j.ajog.2005.01.034] [PMID: 16098858]
[32]
Signorile PG, Severino A, Santoro M, Spyrou M, Viceconte R, Baldi A. Methylation analysis of HOXA10 regulatory elements in patients with endometriosis. BMC Res Notes 2018; 11(1): 722.
[http://dx.doi.org/10.1186/s13104-018-3836-1] [PMID: 30309386]
[33]
Izawa M, Taniguchi F, Uegaki T, et al. Demethylation of a nonpromoter cytosine-phosphate-guanine island in the aromatase gene may cause the aberrant up-regulation in endometriotic tissues. Fertil Steril 2011; 95(1): 33-9.
[http://dx.doi.org/10.1016/j.fertnstert.2010.06.024] [PMID: 20655525]
[34]
Zhao W, Kang S, Zhao J, Wang L, Cao S, Li Y. Aberrant methylation of the IL-12B promotor region contributes to the risk of developing ovarian endometriosis. Mol Reprod Dev 2019; 86(6): 632-8.
[http://dx.doi.org/10.1002/mrd.23139] [PMID: 30865360]
[35]
Bulun SE, Monsavais D, Pavone ME, et al. Role of estrogen receptor-β in endometriosis. Semin Reprod Med 2012; 30(1): 39-45.
[http://dx.doi.org/10.1055/s-0031-1299596] [PMID: 22271293]
[36]
Zhao J, Wang L, Li Y, Zhao W, Kang S. Hypomethylation of the GSTM1 promoter is associated with ovarian endometriosis. Hum Reprod 2019; 34(5): 804-12.
[http://dx.doi.org/10.1093/humrep/dez039] [PMID: 30989213]
[37]
Tamaresis JS, Irwin JC, Goldfien GA, et al. Molecular classification of endometriosis and disease stage using high-dimensional genomic data. Endocrinology 2014; 155(12): 4986-99.
[http://dx.doi.org/10.1210/en.2014-1490] [PMID: 25243856]
[38]
ZR T R Z, ZX L, SL D, K Y. Estrogen-Receptor Expression and Function in Female Reproductive Disease. Cells 2019; 8(10)
[39]
Fujimoto J, Hirose R, Sakaguchi H, Tamaya T. Expression of oestrogen receptor-α and -β in ovarian endometriomata. Mol Hum Reprod 1999; 5(8): 742-7.
[http://dx.doi.org/10.1093/molehr/5.8.742] [PMID: 10421802]
[40]
Cavallini A, Resta L, Caringella AM, Dinaro E, Lippolis C, Loverro G. Involvement of estrogen receptor-related receptors in human ovarian endometriosis. Fertil Steril 2011; 96(1): 102-6.
[http://dx.doi.org/10.1016/j.fertnstert.2011.04.032] [PMID: 21561608]
[41]
Fazleabas AT, Brudney A, Chai D, Langoi D, Bulun SE. Steroid receptor and aromatase expression in baboon endometriotic lesions. Fertil Steril 2003; 80(Suppl. 2): 820-7.
[http://dx.doi.org/10.1016/S0015-0282(03)00982-8] [PMID: 14505759]
[42]
Bulun SE, Cheng YH, Yin P, et al. Progesterone resistance in endometriosis: link to failure to metabolize estradiol. Mol Cell Endocrinol 2006; 248(1-2): 94-103.
[http://dx.doi.org/10.1016/j.mce.2005.11.041] [PMID: 16406281]
[43]
Jichan Nie, Xishi Liu, Guo SW. Promoter hypermethylation of progesterone receptor isoform B (PR-B) in adenomyosis and its rectification by a histone deacetylase inhibitor and a demethylation agent. Reprod Sci 2010; 17(11): 995-1005.
[http://dx.doi.org/10.1177/1933719110377118] [PMID: 20697142]
[44]
Wu Y, Starzinski-Powitz A, Guo SW. Prolonged stimulation with tumor necrosis factor-alpha induced partial methylation at PR-B promoter in immortalized epithelial-like endometriotic cells. Fertil Steril 2008; 90(1): 234-7.
[http://dx.doi.org/10.1016/j.fertnstert.2007.06.008] [PMID: 17727850]
[45]
Wu Y, Shi X, Guo SW. The knockdown of progesterone receptor isoform B (PR-B) promotes proliferation in immortalized endometrial stromal cells. Fertil Steril 2008; 90(4): 1320-3.
[http://dx.doi.org/10.1016/j.fertnstert.2007.10.049] [PMID: 18249378]
[46]
Taylor HS, Arici A, Olive D, Igarashi P. HOXA10 is expressed in response to sex steroids at the time of implantation in the human endometrium. J Clin Invest 1998; 101(7): 1379-84.
[http://dx.doi.org/10.1172/JCI1597] [PMID: 9525980]
[47]
Fambrini M, Sorbi F, Bussani C, Cioni R, Sisti G, Andersson KL. Hypermethylation of HOXA10 gene in mid-luteal endometrium from women with ovarian endometriomas. Acta Obstet Gynecol Scand 2013; 92(11): 1331-4.
[http://dx.doi.org/10.1111/aogs.12236] [PMID: 24032603]
[48]
Andersson KL, Bussani C, Fambrini M, et al. DNA methylation of HOXA10 in eutopic and ectopic endometrium. Hum Reprod 2014; 29(9): 1906-11.
[http://dx.doi.org/10.1093/humrep/deu161] [PMID: 24963168]
[49]
Lu H, Yang X, Zhang Y, Lu R, Wang X. Epigenetic disorder may cause downregulation of HOXA10 in the eutopic endometrium of fertile women with endometriosis. Reprod Sci 2013; 20(1): 78-84.
[http://dx.doi.org/10.1177/1933719112451146] [PMID: 22915150]
[50]
Rice DA, Mouw AR, Bogerd AM, Parker KL. A shared promoter element regulates the expression of three steroidogenic enzymes. Mol Endocrinol 1991; 5(10): 1552-61.
[http://dx.doi.org/10.1210/mend-5-10-1552] [PMID: 1775136]
[51]
Yamagata Y, Nishino K, Takaki E, et al. Genome-wide DNA methylation profiling in cultured eutopic and ectopic endometrial stromal cells. PLoS One 2014; 9(1) e83612.
[http://dx.doi.org/10.1371/journal.pone.0083612] [PMID: 24465385]
[52]
Q X YF Z, SN Z, SE B. Hypermethylation of the CpG island spanning from exon II to intron III is associated with steroidogenic factor 1 expression in stromal cells of endometriosis. Reproductive Sciences (thousand oaks, calif) 2011; 18(11): 1080-4.
[53]
Xue Q, Xu Y, Yang H, et al. Methylation of a novel CpG island of intron 1 is associated with steroidogenic factor 1 expression in endometriotic stromal cells. Reprod Sci 2014; 21(3): 395-400.
[http://dx.doi.org/10.1177/1933719113497283] [PMID: 23899549]
[54]
Min H, Yao J, Cai Li, Bachman KE. Frederic vdB, Victor V. Polyak K. Distinct epigenetic changes in the stromal cells of breast cancers. Nature Genetics 2005; 37(8): 899-905.
[55]
Hatok J, Zubor P, Galo S, et al. Endometrial aromatase mRNA as a possible screening tool for advanced endometriosis and adenomyosis. Gynecol Endocrinol 2011; 27(5): 331-6.
[http://dx.doi.org/10.3109/09513590.2010.491925] [PMID: 20553220]
[56]
Izawa M, Harada T, Taniguchi F, Ohama Y, Takenaka Y, Terakawa N. An epigenetic disorder may cause aberrant expression of aromatase gene in endometriotic stromal cells. Fertil Steril 2008; 89(5)(Suppl.): 1390-6.
[http://dx.doi.org/10.1016/j.fertnstert.2007.03.078] [PMID: 17662285]
[57]
Szczepańska M, Wirstlein P, Luczak M, Jagodziński PP, Skrzypczak J. Reduced expression of HOXA10 in the midluteal endometrium from infertile women with minimal endometriosis. Biomed Pharmacother 2010; 64(10): 697-705.
[http://dx.doi.org/10.1016/j.biopha.2010.09.012] [PMID: 20971605]
[58]
Naqvi H, Ilagan Y, Krikun G, Taylor HS. Altered genome-wide methylation in endometriosis. Reprod Sci 2014; 21(10): 1237-43.
[http://dx.doi.org/10.1177/1933719114532841] [PMID: 24784717]
[59]
Makabe T, Arai E, Hirano T, et al. Genome-wide DNA methylation profile of early-onset endometrial cancer: its correlation with genetic aberrations and comparison with late-onset endometrial cancer. Carcinogenesis 2019; 40(5): 611-23.
[http://dx.doi.org/10.1093/carcin/bgz046] [PMID: 30850842]
[60]
Barjaste N, Shahhoseini M, Afsharian P. Sharifi- Zarchi A, Masoudi-Nejad A. Genome-wide DNA methylation profiling in ectopic and eutopic of endometrial tissues. J Assist Reprod Genet 2019.
[http://dx.doi.org/10.1007/s10815-019-01508-8]
[61]
Osaki M, Oshimura MA, Ito H. PI3K-Akt pathway: its functions and alterations in human cancer. Apoptosis 2004; 9(6): 667-76.
[62]
Fukuda M. Roles of mucin-type O-glycans in cell adhesion. Biochim Biophys Acta 2002; 1573(3): 394-405.
[http://dx.doi.org/10.1016/S0304-4165(02)00409-9] [PMID: 12417424]
[63]
Jaroslaw Paluszczak WB-D. Epigenetic diagnostics of cancer – the application ofDNA methylation markers. J Appl Genet 2006; 365-75.
[http://dx.doi.org/10.1007/BF03194647]
[64]
Belinsky SA, Klinge DM, Dekker JD, et al. Gene promoter methylation in plasma and sputum increases with lung cancer risk. Clin Cancer Res 2005; 11(18): 6505-11.
[http://dx.doi.org/10.1158/1078-0432.CCR-05-0625] [PMID: 16166426]
[65]
Guo SW. Epigenetics of endometriosis. Mol Hum Reprod 2009; 15(10): 587-607.
[http://dx.doi.org/10.1093/molehr/gap064] [PMID: 19651637]
[66]
Ferrero S, Evangelisti G, Barra F. Current and emerging treatment options for endometriosis. Expert Opin Pharmacother 2018; 19(10): 1109-25.
[http://dx.doi.org/10.1080/14656566.2018.1494154] [PMID: 29975553]
[67]
Ferrero S, Barra F, Leone Roberti Maggiore U. Current and Emerging Therapeutics for the Management of Endometriosis. Drugs 2018; 78(10): 995-1012.
[http://dx.doi.org/10.1007/s40265-018-0928-0] [PMID: 29946962]
[68]
Parazzini F, Bertulessi C, Pasini A, et al. Gruppo Italiano di Studio Endometriosi. Determinants of short term recurrence rate of endometriosis. Eur J Obstet Gynecol Reprod Biol 2005; 121(2): 216-9.
[http://dx.doi.org/10.1016/j.ejogrb.2004.11.033] [PMID: 16054965]
[69]
Eleftheria Hatzimichael KL. Van Ren Sim, Evangelos Briasoulis, Tim Crook. Epigenetics in diagnosis, prognostic assessment and treatment of cancer: An update. EXCLI J 2014; 954-76.
[70]
Nasu K, Kawano Y, Tsukamoto Y, et al. Aberrant DNA methylation status of endometriosis: epigenetics as the pathogenesis, biomarker and therapeutic target. J Obstet Gynaecol Res 2011; 37(7): 683-95.
[http://dx.doi.org/10.1111/j.1447-0756.2011.01663.x] [PMID: 21651673]
[71]
Colón-Caraballo M, Torres-Reverón A, Soto-Vargas JL, et al. Effects of histone methyltransferase inhibition in endometriosis. Biol Reprod 2018; 99(2): 293-307.
[http://dx.doi.org/10.1093/biolre/ioy030] [PMID: 29408993]
[72]
Cheishvili D, Boureau L, Szyf M. DNA demethylation and invasive cancer: implications for therapeutics. Br J Pharmacol 2015; 172(11): 2705-15.
[http://dx.doi.org/10.1111/bph.12885] [PMID: 25134627]
[73]
Huang D, Cui L, Ahmed S, et al. An overview of epigenetic agents and natural nutrition products targeting DNA methyltransferase, histone deacetylases and microRNAs. Food Chem Toxicol 2019; 123: 574-94.
[http://dx.doi.org/10.1016/j.fct.2018.10.052] [PMID: 30408543]
[74]
Egger G, Liang G, Aparicio A, Jones PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature 2004; 429(6990): 457-63.
[http://dx.doi.org/10.1038/nature02625] [PMID: 15164071]
[75]
Wang X, Wang H, Jiang N, Lu W, Zhang XF, Fang JY. Effect of inhibition of MEK pathway on 5-aza-deoxycytidine-suppressed pancreatic cancer cell proliferation. Genet Mol Res 2013; 12(4): 5560-73.
[http://dx.doi.org/10.4238/2013.November.18.6] [PMID: 24301926]
[76]
Katz TA, Vasilatos SN, Harrington E, Oesterreich S, Davidson NE, Huang Y. Inhibition of histone demethylase, LSD2 (KDM1B), attenuates DNA methylation and increases sensitivity to DNMT inhibitor-induced apoptosis in breast cancer cells. Breast Cancer Res Treat 2014; 146(1): 99-108.
[http://dx.doi.org/10.1007/s10549-014-3012-9] [PMID: 24924415]
[77]
Ateeq B, Unterberger A, Szyf M, Rabbani SA. Pharmacological inhibition of DNA methylation induces proinvasive and prometastatic genes in vitro and in vivo. Neoplasia 2008; 10(3): 266-78.
[http://dx.doi.org/10.1593/neo.07947] [PMID: 18320071]
[78]
Wang L, Tan YJ, Wang M, Chen YF, Li XY. DNA Methylation Inhibitor 5-Aza-2′-Deoxycytidine Modulates Endometrial Receptivity Through Upregulating HOXA10 Expression. Reprod Sci 2019; 26(6): 839-46.
[http://dx.doi.org/10.1177/1933719118815575] [PMID: 30522400]
[79]
S. Taylor H. The role of HOXgenes in human implantation. European Society ofHuman Reproduction and Embryology 2000; 6: 75-9.
[80]
Hirakawa T, Nasu K, Aoyagi Y, Takebayashi K, Zhu R, Narahara H. ATM expression is attenuated by promoter hypermethylation in human ovarian endometriotic stromal cells. Mol Hum Reprod 2019; 25(6): 295-304.
[http://dx.doi.org/10.1093/molehr/gaz016] [PMID: 30869775]
[81]
Arosh JA, Lee J, Starzinski-Powitz A, Banu SK. Selective inhibition of prostaglandin E2 receptors EP2 and EP4 modulates DNA methylation and histone modification machinery proteins in human endometriotic cells. Mol Cell Endocrinol 2015; 409: 51-8.
[http://dx.doi.org/10.1016/j.mce.2015.03.023] [PMID: 25843056]
[82]
Kantarjian HM, Thomas XG, Dmoszynska A, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol 2012; 30(21): 2670-7.
[http://dx.doi.org/10.1200/JCO.2011.38.9429] [PMID: 22689805]
[83]
Mikyšková R, Indrová M, Vlková V, et al. DNA demethylating agent 5-azacytidine inhibits myeloid-derived suppressor cells induced by tumor growth and cyclophosphamide treatment. J Leukoc Biol 2014; 95(5): 743-53.
[http://dx.doi.org/10.1189/jlb.0813435] [PMID: 24389335]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 21
ISSUE: 11
Year: 2020
Page: [1047 - 1055]
Pages: 9
DOI: 10.2174/1389450121666200228112344
Price: $65

Article Metrics

PDF: 25
HTML: 5