Journal of Shandong University (Health Sciences) ›› 2021, Vol. 59 ›› Issue (7): 1-9.doi: 10.6040/j.issn.1671-7554.0.2021.0055

   

Expressions of DNA methyltransferases in gastric cancer and their clinical significance

CHU Yan1,2, LIU Duanrui1,2, ZHU Wenshuai1,2, FAN Rong1,2, MA Xiaoli1, WANG Yunshan1, JIA Yanfei1   

  1. 1. Research Center of Basic Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250013, Shandong, China;
    2. Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China
  • Published:2021-07-16

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Abstract: Objective To investigate the expressions of DNA methyltransferases(DNMT1, DNMT3A, DNMT3B)in gastric cancer and its correlation with the clinicopathological parameters and prognosis of gastric cancer. Methods Based on TCGA and GEO data, the differences in DNA methyltransferases expressions were compared between gastric cancer and adjacent normal tissues; the effects of DNA methyltransferases on the prognosis of patients with gastric cancer were analyzed with Kaplan-Meier plotter; the relationship between DNA methyltransferases and clinicopathological parameters was analyzed; the biological function of DNMT3B was explored with gene enrichment analysis(GSEA)binding protein interaction network. The mechanism of DNMT3B elevation in the progression of gastric cancer was also analyzed. Results The expressions of three DNA methyltransferases in gastric cancer tissues were higher than those in adjacent normal tissues; survival analysis showed that patients with high expressions of DNMT3A and DNMT3B had shorter overall survival; DNMT3B expression was related to the histological type, and was high in intestinal type gastric cancer; Helicobacter pylori infection promoted the expression of DNMT3B; DNMT3B promoted the progression of gastric cancer by affecting the methylation of BUB1 and HDAC2. Conclusion DNA methyltransferases are highly expressed in gastric cancer. DNMT3B is a prognostic indicator of gastric cancer and may be a biomarker for the clinical diagnosis and treatment of gastric cancer.

Key words: DNA methyltransferase, Gastric cancer, Prognosis, TCGA database, GEO database

CLC Number: 

  • R735.2
[1] Karimi P, Islami F, Anandasabapathy S, et al. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention[J]. Cancer Epidemiol Biomarkers Prev, 2014, 23(5): 700-713.
[2] 王攀, 赵洪林, 任凡, 等. 表观遗传学在恶性肿瘤发生发展和治疗中的新进展[J]. 中国肺癌杂志, 2020, 23(2): 91-100. WANG Pan, ZHAO Honglin, REN Fan, et al. New progress of epigenetics in the occurrence, development and treatment of malignant tumors [J]. Chinese Journal of Lung Cancer, 2020, 23(2): 91-100.
[3] 杨梦迪, 王学红, 张梅. 表观遗传学在胃癌中的研究进展[J]. 癌症进展, 2019, 17(5): 503-506. YANG Mengdi, WANG Xuehong, ZHANG Mei. Research progress of epigenetics in gastric cancer [J]. Cancer Progress, 2019, 17(5): 503-506.
[4] 赵琦, 相绿竹, 彭瑞, 等. DNA及RNA甲基化检测在肿瘤诊断中的研究进展[J]. 国际检验医学杂志, 2019, 40(11): 1356-1360. ZHAO Qi, XIANG Lüzhu, PENG Rui, et al. Research progress of DNA and RNA methylation detection in tumor diagnosis [J]. International Journal of Laboratory Medicine, 2019, 40(11): 1356-1360.
[5] 肖枭, 王艳林, 黄利鸣. DNA甲基转移酶与肿瘤关系的研究进展[J]. 生命科学, 2019, 31(1): 87-92. XIAO Xiao, WANG Yanlin, HUANG Liming. Research progress on the relationship between DNA methyltransferase and tumor [J]. Life Sciences, 2019, 31(1): 87-92.
[6] Giri AK, Aittokallio T. DNMT inhibitors increase methylation in the cancer genome [J]. Front Pharmacol, 2019, 10: 385. doi: 10.3389/fphar.2019.00385.
[7] Cristina S, José-Enériz ES, Maravilla EM, et al. Inhibition of a G9a/DNMT network triggers immune-mediated bladder cancer regression [J]. Nat Med, 2019, 25(7): 1073-1081.
[8] 李含含, 段圆圆, 刘美君, 等. miR-142靶向DNMT1抑制乳腺癌细胞的迁移[J]. 生物技术, 2020, 30(1): 75-81. LI Hanhan, DUAN Yuanyuan, LIU Meijun, et al. miR-142 targeting DNMT1 inhibits the migration of breast cancer cells [J]. Biotechnology, 2020, 30(1): 75-81.
[9] Li SX, Han ZP, Zhao NP, et al. Inhibition of DNMT suppresses the stemness of colorectal cancer cells through down-regulating Wnt signaling pathway [J]. Cell Signal, 2018, 47: 79-87. doi: 10.1016/j.cellsig.2018.03.014.
[10] Wang LH, Huang J, Wu CR, et al. Downregulation of miR-29b targets DNMT3b to suppress cellular apoptosis and enhance proliferation in pancreatic cancer [J]. Mol Med Rep, 2018, 17(2): 2113-2120.
[11] 王震凯, 杨晓倩, 叶雅沁, 等. DNA甲基转移酶在胃癌中的表达及其意义[J]. 胃肠病学, 2019, 24(2): 81-85. WANG Zhenkai, YANG Xiaoqian, YE Yaqin, et al. Expression and significance of DNA methyltransferase in gastric cancer [J]. Gastroenterology, 2019, 24(2): 81-85.
[12] Wu S, Xie J, Shi H, et al. miR-492 promotes chemoresistance to CDDP and metastasis by targeting inhibiting DNMT3B and induces stemness in gastric cancer [J]. Biosci Rep, 2020, 40(3): BSR20194342. doi: 10.1042/BSR20194342.
[13] 殷科, 盛贤能, 郭宇, 等. DNMT1、DNMT3B在胃癌中的表达及其临床意义[J].现代实用医学, 2013, 25(12): 1386-1388. YIN Ke, SHENG Xianneng, GUO Yu, et al. Expression and clinical significance of DNMT1、DNMT3Bin gastric cancer [J]. Modern Practical Medicine, 2013, 25(12): 1386-1388.
[14] Venerito M, Alexander L, Rokkas T, et al. Gastric cancer-clinical and epidemiological aspects [J]. Helicobacter, 2016, 21(Suppl 1): 39-44.
[15] Guggenheim DE, Shah MA. Gastric cancer epidemiology and risk factors [J]. J Surg Oncol, 2013, 107(3): 230-236.
[16] 王永云, 靳文, 俞兰. 胃癌相关基因及靶向治疗的研究进展[J]. 医学综述, 2020, 26(19): 3814-3819. WANG Yongyun, JIN Wen, YU Lan. Research progress of gastric cancer related genes and targeted therapy[J]. Medical Review, 2020, 26(19): 3814-3819.
[17] 纪艺珍,张瑞晴,张佳荣. DNA甲基化在女性正常妊娠与输卵管妊娠中的作用[J]. 检验医学与临床, 2017, 14(17): 2643-2645. JI Yizhen, ZHANG Ruiqing, ZHANG Jiarong. The role of DNA methylation in female normal pregnancy and tubal pregnancy [J]. Laboratory Medicine and Clinical, 2017, 14(17): 2643-2645.
[18] Moore LD, Le T, Fan G. DNA methylation and its basic function [J]. Neuropsychopharmacology, 2013, 38(1): 23-38.
[19] Frank Lyko. The DNA methyltransferase family: a versatile toolkit for epigenetic regulation [J]. Nat Rev Genet, 2018, 19(2): 81-92.
[20] Zhang ZM, Lu R, Wang P, et al. Structural basis for DNMT3A-mediated de novo DNA methylation [J]. Nature, 2018, 554(7692): 387-391.
[21] Tajima S, Suetake I, Takeshita K, et al. Domain structure of the DNMT1, DNMT3A, and DNMT3B DNA methyltransferases [J]. Adv Exp Med Biol, 2016, 945: 63-86. doi: 10.1007/978-3-319-43624-1_4.
[22] Cao XY, Ma HX, Shang YH, et al. DNA methyltransferase3a expression is an independent poor prognostic indicator in gastric cancer [J]. World J Gastroenterol, 2014, 20(25): 8201-8208.
[23] 李小燕,何杰,余觅,等 BUB1基因在胃癌组织中高表达:基于Oncomine数据库及生物信息学方法[J].南方医科大学学报,2020,40(5):683-692. LI Xiaoyan, HE Jie, YU Mi, et al. BUB1 gene is highlyexpressed in gastric cancer:analysis based on Oncominedatabase and bioinformatics[J]. Journal of Southern Medical University, 2020, 40(5): 683-692.
[24] Zhu LJ, Pan Y, Chen XY, et al. BUB1 promotes proliferation of liver cancer cells by activating SMAD2 phosphorylation [J]. Oncol Lett, 2020, 19(5): 3506-3512.
[25] Feng H, Gu ZY, Li Q, et al. Identification of significant genes with poor prognosis in ovarian cancer via bioinformatical analysis [J]. J Ovarian Res, 2019, 12(1): 35.
[26] Tang W, Zhou W, Xiang L, et al. The p300/YY1/miR-500a-5p/HDAC2 signalling axis regulates cell proliferation in human colorectal cancer [J]. Nat Commun, 2019, 10(1): 663.
[27] 王玉芝. TRPS1调控HDAC2在乳腺癌中的作用和机制研究[D]. 南京: 东南大学, 2018.
[28] Qi ZP, Yalikong A, Zhang JW, et al. HDAC2 promotes the EMT of colorectal cancer cells and via the modular scaffold function of ENSG00000274093.1 [J]. J Cell Mol Med, 2021, 25(2): 1190-1197.
[29] Zhou Z, Li HQ, Liu F. DNA Methyltransferase Inhibitors and their Therapeutic Potential [J]. Curr Top Med Chem, 2018, 18(28): 2448-2457.
[30] Da Costa EM, McInnes G, Beaudry A, et al. DNA Methylation-Targeted Drugs [J]. Cancer J, 2017, 23(5): 270-276.
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