JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2017, Vol. 55 ›› Issue (1): 44-48.doi: 10.6040/j.issn.1671-7554.0.2016.942

Previous Articles     Next Articles

Role of methylation status of the cyclooxygenase-2 gene promoter in endometriosis

CHEN Qi1, LI Jiaqi1, GUO Zhibin2, JIA Jingyu3, HE Linsheng1   

  1. 1. Department of Obstetrics &
    Gynecology, the First Affiliated Hospital of Nanchang University;
    2. Deaprtment of Central Laboratory, Childrens Hospital of Jiangxi Province;
    3. Department of Orthopedics, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China
  • Received:2016-08-03 Online:2017-01-10 Published:2017-01-10

PDF (PC)

337

Abstract: Objective To study the methylation status of CRE sites in the cyclooxygenase-2(COX-2)gene promoter and its correlationship with endometriosis(EMs). Methods The endometrial tissues were collected from 40 women with laparoscopically confirmed EMs(case group), and 40 women without EMs(control group). The methylation status of COX-2 was examined by pyrosequencing. Quantitative real-time RT-PCR and immunohistochemistry were respectively performed to measure mRNA expression levels and protein levels of COX-2 in endometrial tissues. Finally, the correlation between COX-2 expression level and methylation frequencies of CRE sites were analyzed. Results The methylation frequencies of CRE sites in the COX-2 gene promoter was higher in the control group(40.81%±6.10%)than that in the case group(14.74%±2.84%), P<0.05. COX-2 mRNA levels(0.98±0.37)and protein levels(1.00±0.73)in the control group was significantly lower than the mRNA levels(2.63±0.44)and protein levels 山 东 大 学 学 报 (医 学 版)55卷1期 -陈琦,等.环氧化酶-2基因启动子区甲基化水平在子宫内膜异位症中的作用 \=-(2.74±1.18)in the case group, both P<0.05. The correlation between COX-2 expression levels and methylation frequencies of CRE sites in the COX-2 gene promoter was negative(P<0.05). Conclusion The hypomethylation of CRE sites within the promoter of COX-2 may be responsible for the elevated gene expression in eutopic endometrium of EMs.

Key words: Endometriosis, Cyclooxygenase-2, CRE sites, Methylation

CLC Number: 

  • R711.71
[1] Bulun SE. Endometriosis[J]. N Engl J Med, 2009, 360(3): 268-279.
[2] Vinatier D, Cosson M, Dufour P. Is endometriosis an endometrial disease? [J]. Eur J Obstet Gynecol Reprod Biol, 2000, 91(2):113-125.
[3] Dubois RN, Abramson SB, Crofford L, et al. Cyclooxygenase in biology and disease[J]. FASEB J, 1998, 12(12):1063-1073.
[4] Chen Q, Zhang C, Chen Y, et al. Identification of endometriosis-related genes by representational difference analysis of cDNA[J]. Aust N Z J Obstet Gynaecol, 2012, 52(2):140-145.
[5] Huang F, Cao J, Liu Q, et al. MAPK/ERK signal pathway involved expression of COX-2 and VEGF by IL-1β induced in human endometriosis stromal cells in vitro[J]. Int J Clin Exp Pathol, 2013, 6(10):2129-2136.
[6] Khan KN, Kitajima M, Fujishita A, et al. Pelvic pain in women with ovarian endometrioma is mostly associated with coexisting peritoneal lesions[J]. Hum Reprod, 2013, 28(1):109-118.
[7] Cavalcanti V, Ponce TG, Mafra FA, et al. Evaluation of the frequency of G-765C polymorphism in the promoter region of the COX-2 gene and its correlation with the expression of this gene in the endometrium of women withendometriosis[J]. Arch Gynecol Obstet, 2016, 293(1):109-115.
[8] Feinberg AP. Phenotypic plasticity and the epigenetics of human disease[J]. Nature, 2007, 447(7143):433-440.
[9] Feinberg AP. Epigenetics at the epicenter of modern medicine[J]. JAMA, 2008, 299(11):1345-1350.
[10] Guo SW. Epigenetics of endometriosis[J]. Mol Hum Reprod, 2009, 15(10):587-607.
[11] Xu XL, Yu J, Zhang HY, et al. Methylation profile of the promoter CpG islands of 31 genes that may contribute to colorectal carcinogenesis[J]. World J Gastroenterol, 2004, 10(23):3441-3454.
[12] Lee S, Hwang KS, Lee HJ, et al. Aberrant CpG island hypermethylation of multiple genes in colorectal neoplasia[J]. Lab Invest, 2004, 84(7):884-893.
[13] Chow LW, Zhu L, Loo WT, et al. Aberrant methylation of cyclooxygenase-2 in breast cancer patients[J]. Biomed Pharmacother, 2005, 59(Suppl 2):S264-S267.
[14] Inoue H, Yokoyama C, Hara S, et al. Transcriptional regulation of human prostaglandin-endoperoxide synthase-2 gene by lipopolysaccharide and phorbol ester in vascular endothelial cells. Involvement of both nuclear factor for interleukin-6 expression site and cAMP response element[J]. J Biol Chem, 1995, 270(42):24965-24971.
[15] Inoue H, Tanabe T. Transcriptional role of the nuclear factor kappa B site in the induction by lipopolysaccharide and suppression by dexamethasone of cyclooxygenase-2 in U937 cells[J]. Biochem Biophys Res Commun, 1998, 244(1):143-148.
[16] Wang D, Chen Q, Zhang C, et al. DNA hypomethylation of the COX-2 gene promoter is associated with up-regulation of its mRNA expression in eutopic endometrium of endometriosis[J]. Eur J Med Res, 2012, 17(1):12.
[17] Zidan HE, Rezk NA, Alnemr AA, et al. COX-2 gene promoter DNA methylation status in eutopic and ectopic endometrium of Egyptian women with endometriosis[J]. J Reprod Immunol, 2015, 112: 63-67.
[18] Lee B, Dziema H, Lee KH, et al. CRE-mediated transcription and COX-2 expression in the pilocarpine model of statusepilepticus[J]. Neurobiol Dis, 2007, 25(1): 80-91.
[19] Mouawad CA, Mrad MF, El-Achkar GA, et al. Statins modulate cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in human hepatic myofibroblasts[J]. J Cell Biochem, 2016, 117(5): 1176-1186.
[20] Kim SY, Hwang JS, Han IO. Tunicamycin inhibits Toll-like receptor-activated inflammation in RAW264.7 cells by suppression of NF-κB and c-Jun activity via a mechanism that is independent of ER-stress and N-glycosylation[J]. Eur J Pharmacol, 2013, 721(1-3): 294-300.
[21] Sharma-Walia N, George Paul A, Patel K, et al. NFAT and CREB regulate Kaposis sarcoma-associated herpesvirus-induced cyclooxygenase2(COX-2)[J]. J Virol, 2010, 84(24):12733-12753.
[22] Ohlsson Teague EM, Van der Hoek KH, Van der Hoek MB, et al. MicroRNA-regulated pathways associated with endometriosis[J]. Mol Endocrinol, 2009, 23(2):265-275.
[23] Zhou Y, Zeng C, Li X, et al. IGF-I stimulates ERβ and aromatase expression via IGF1R/PI3K/AKT-mediated transcriptional activation inendometriosis[J]. J Mol Med(Berl), 2016, 94(8):887-897.
[24] Hibi K, Taguchi M, Nakayama H, et al. Molecular detection of p16 promoter methylation in the serum of patients with esophageal squamous cell carcinoma[J]. Clin Cancer Res, 2001, 7(10):3135-3138.
[25] Tomizawa Y, Kohno T, Kondo H, et al. Clinicopathological significance of epigenetic inactivation of RASSF1A at 3p21.3 in stage I lung adenocarcinoma[J]. Clin Cancer Res, 2002, 8(7):2362-2368.
[26] Fischer JR, Ohnmacht U, Rieger N, et al. Promoter methylation of RASSFIA, RARbeta and DAPK predict poor prognosis of patient, with malignant mesothelioma[J]. Lung Cancer, 2006, 54(1):109-116.
[1] ZHOU Xue, WANG Yanrong, TIAN Long, MA Lianghong, YAN Bei, TIAN Jia, ZHANG Fan, ZHOU Yue, WANG Hongyan. DNA methylation and expression of SNRPN and GRB10 imprinted genes in human semen freezing-thawing process [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(1): 54-59.
[2] YANG Yanjun, LIANG Jing, LI Fang, DU Lingxi. Effect of halofuginone on macrophage polarization in endometriosis mouse [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(9): 26-31.
[3] YANG Juan, QIU Zongjian, SONG Qiang. Impacts of Simvastatin on DNA methyltransferase of cell line NB4 in acute myeloid leukemia [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(6): 28-32.
[4] REN Hongbo, LIU Hainan, LIU Cheng, YAN Keqiang, XIA Chuanyou, FAN Yidong. Clinical significance of human telomerase reverse transcriptase gene methylation status in urine sediments of renal cell carcinoma [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(1): 73-76.
[5] ZHAO Yongqiang, XIE Xiaoye, CHEN Xuemei, FENG Huiwei, JIA Tao, ZHANG Hui, FAN Xianliang. COX-2 specific inhibitor induced apoptosis and autophagy in Hep-2 cells in vitro [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(9): 39-43.
[6] LI Hongli, WANG Yan, XU Wenwei, DONG Lin, GUO Yan, ZHU Chuansheng, BI Kehong. Changes of NF-κB expression after promoter demethylation of TMS1 in K562 cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(4): 62-66.
[7] FAN Hai-yan， ZHANG Hui-jing， GUO Zhan-jun， LI Sheng-mian. Prognostic significance of RASSF1A and WIF-1 methylation in the cancer tissues of patients with HCC [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(5): 89-93.
[8] CHEN Yan1, LI Dong2, ZHANG Zhe1, SHI Qing2, WANG Da-kun2, LIU Huan2, WANG Guo-yun1. Effects of human umbilical cord mesenchymal stem cells on nerve fibers in the lesions of rat endometriosis  model [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(3): 48-51.
[9] YU Ling, TIAN Yong-jie. Clinical study of the related  risk factors associated with endometriosis  [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(2): 79-83.
[10] WANG Xiao-lei1， GAO Ling1, YU Chun-xiao1, LIU Yuan-tao2， ZHANG Nan1, GUAN Qing-bo1, ZHAO Jia-jun1. Mechanisms involved in hydrogen sulfide attenuating high glucose-induced inflammation in endothelial cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(2): 44-48.
[11] XU Jia, SONG Qiang. Deletion of the RASSF1A gene and promoter methylation in the bone marrow of patients with myelodysplastic syndromes [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(2): 65-69.
[12] HOU Bei-bei, WANG Yan, ZHANG Juan, LIANG Xiao-hui, LI Jin-song. Clinicopathological significances of WIF-1 gene methylation and Wnt-5a protein expression in chondrosarcoma [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(2): 70-74.
[13] XIE Fang, LIU Shuai, LIU Zheng, NIU Zhi-hong. NOV modulates expression of Ki-67,VEGF，p27 and COX-2 in renal clear cell carcinoma [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(10): 29-32.
[14] CHEN Hai-yan, YAO Shu-zhe, ZHANG Xiao-ying, ZHANG Jian-ping, ZHANG Cui-juan, ZHANG Ting-guo. Effect of the methylation of SOCS-3 and 3-OST-2 genes in endometrial cancer and its clinical pathological significances [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(06): 75-80.
[15] ZHU Xun-xun1, ZHU Chuan-sheng2, WANG Yan2, XU Wen-wei2, DONG Lin2, GUO Yan2, LI Hong-li1, BI Ke-hong2　. Analysis of methylation of the Dickkopf1 (DKK1) gene in acute leukemia [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(5): 84-.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd