切换至 "中华医学电子期刊资源库"

中华脑科疾病与康复杂志(电子版) ›› 2021, Vol. 11 ›› Issue (05) : 309 -315. doi: 10.3877/cma.j.issn.2095-123X.2021.05.011

综述

胶质瘤的表观遗传学发展
娜迪热·依明1, 崔红1, 努尔比亚·牙生1, 祖莱娅提·阿不都热依木1, 祖丽凯麦尔·阿布拉江1, 麦麦提力·米吉提1,()   
  1. 1. 830054 乌鲁木齐,新疆医科大学第一附属医院神经外科
  • 收稿日期:2021-11-03 出版日期:2021-10-15
  • 通信作者: 麦麦提力·米吉提

Epigenetic advances in glioma

Yiming Nadire1, Hong Cui1, Yasheng Nuerbiya1, Abudureyimu Zulaiyati1, Abulajiang Zulikaimaier1, Mijiti Maimaitili1,()   

  1. 1. Department of Neurosurgery, the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China
  • Received:2021-11-03 Published:2021-10-15
  • Corresponding author: Mijiti Maimaitili
引用本文:

娜迪热·依明, 崔红, 努尔比亚·牙生, 祖莱娅提·阿不都热依木, 祖丽凯麦尔·阿布拉江, 麦麦提力·米吉提. 胶质瘤的表观遗传学发展[J]. 中华脑科疾病与康复杂志(电子版), 2021, 11(05): 309-315.

Yiming Nadire, Hong Cui, Yasheng Nuerbiya, Abudureyimu Zulaiyati, Abulajiang Zulikaimaier, Mijiti Maimaitili. Epigenetic advances in glioma[J]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2021, 11(05): 309-315.

胶质瘤是原发中枢神经系统最常见的恶性肿瘤,侵袭性强、发病率高,治疗最为复杂且生存率低。目前,胶质瘤的治疗原则是以手术治疗为主,联合术后辅助放射治疗和化学治疗的综合治疗,但预后依然不乐观。神经胶质瘤的发展与DNA甲基化异常、非编码RNA异常、染色质重塑、组蛋白修饰、RNA修饰密切相关。经典遗传学主要关注胶质瘤DNA序列的变化,而表观遗传学不涉及DNA序列的改变。基因的表观遗传修饰具有可逆性,有可能成为胶质瘤的治疗靶点。本文主要就表观遗传修饰在胶质瘤发生、发展中的作用作一综述。

The most common primary central nervous system malignancy is glioma, which is highly invasive, has a high incidence, is the most complex treatment and has a low survival rate. At present, the treatment principle of glioma is mainly surgical treatment combined with postoperative adjuvant radiotherapy and chemotherapy, but the prognosis is still not optimistic. Recent studies have found that the development of glioma is closely related to abnormal DNA methylation, abnormal non-coding RNA, chromatin remodeling, histone modification, and RNA modification. For gliomas, classical genetics focuses on changes in the DNA sequence, while epigenetics does not. The reversibility of epigenetic modification of genes makes it possible to be a therapeutic target for glioma. The role of epigenetic modification in the genesis and development of glioma was reviewed in this paper.

图1 狭义的DNA甲基化示意图
图2 DNA甲基化修饰的共同作用机制是调节基因的表达
表1 与神经胶质瘤DNA甲基化有关的基因
图3 重亚硫酸盐测序
表2 染色质重塑因子在胶质瘤起始细胞发挥的作用
[1]
Zang L, Kondengaden SM, Che F, et al. Potential epigenetic-based therapeutic targets for glioma[J]. Front Mol Neurosci, 2018, 11: 408.
[2]
Waker CA, Lober RM. Brain tumors of glial origin[J]. Adv Exp Med Biol, 2019, 1190: 281-297.
[3]
Janin M, Ortiz-Barahona V, de Moura MC, et al. Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program[J]. Acta Neuropathol, 2019, 138(6): 1053-1074.
[5]
Ciechomska IA, Jayaprakash C, Maleszewska M, et al. Histone modifying enzymes and chromatin modifiers in glioma pathobiology and therapy responses[J]. Adv Exp Med Biol, 2020, 1202: 259-279.
[6]
Morgan AE, Davies TJ, Mc Auley MT. The role of DNA methylation in ageing and cancer[J]. Proc Nutr Soc, 2018, 77(4): 412-422.
[7]
Meng H, Cao Y, Qin J, et al. DNA methylation, its mediators and genome integrity[J]. Int J Biol Sci, 2015, 11(5): 604-617.
[8]
Liu Y, Lang F, Chou FJ, et al. Isocitrate dehydrogenase mutations in glioma: genetics, biochemistry, and clinical indications[J]. Biomedicines, 2020, 8(9): 294.
[9]
Noushmehr H, Weisenberger DJ, Diefes K, et al. Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma[J]. Cancer Cell, 2010, 17(5): 510-522.
[10]
Su R, Dong L, Li C, et al. R-2HG exhibits anti-tumor activity by targeting FTO/m6A/MYC/CEBPA signaling[J]. Cell, 2018, 172(1-2): 90-105.e23.
[11]
王振. MGMT基因启动子甲基化及IDH1基因突变在胶质瘤中的临床意义及预后价值[D]. 大连: 大连医科大学, 2017.
[12]
Watanabe T, Huang H, Nakamura M, et al. Methylation of the p73 gene in gliomas[J]. Acta Neuropathol, 2002, 104(4): 357-362.
[13]
Jiang Z, Li X, Hu J, et al. Promoter hypermethylation-mediated down-regulation of LATS1 and LATS2 in human astrocytoma[J]. Neurosci Res, 2006, 56(4): 450-458.
[14]
姜政,周伟,李新钢, 等. 人脑胶质瘤中EMP3和PCDH-γ-A11基因的甲基化调控[J]. 中华外科杂志, 2010, 48(4): 300-304.
[15]
Weller M. Assessing the MGMT status in glioblastoma: one step forward, two steps back?[J]. Neuro Oncol, 2013, 15(3): 253-254.
[16]
Hua XM, Wang J, Qian DM, et al. DNA methylation level of promoter region of activating transcription factor 5 in glioma[J]. J Zhejiang Univ Sci B, 2015, 16(9): 757-762.
[17]
Duncan CG, Barwick BG, Jin G, et al. A heterozygous IDH1R132H/WT mutation induces genome-wide alterations in DNA methylation[J]. Genome Res, 2012, 22(12): 2339-2355.
[18]
Bai Y, Zhang QG, Wang XH. Downregulation of TES by hypermethylation in glioblastoma reduces cell apoptosis and predicts poor clinical outcome[J]. Eur J Med Res, 2014, 19(1): 66.
[19]
Wang S, Shi X, Wei S, et al. Krüppel-like factor 4 (KLF4) induces mitochondrial fusion and increases spare respiratory capacity of human glioblastoma cells[J]. J Biol Chem, 2018, 293(17): 6544-6555.
[20]
Zhou D, Wan Y, Xie D, et al. DNMT1 mediates chemosensitivity by reducing methylation of miRNA-20a promoter in glioma cells[J]. Exp Mol Med, 2015, 47(9): e182.
[21]
Shan ZN, Tian R, Zhang M, et al. miR128-1 inhibits the growth of glioblastoma multiforme and glioma stem-like cells via targeting BMI1 and E2F3[J]. Oncotarget, 2016, 7(48): 78813-78826.
[22]
Fukushima T, Kawaguchi M, Yamamoto K, et al. Aberrant methylation and silencing of the SPINT2 gene in high-grade gliomas[J]. Cancer Sci, 2018, 109(9): 2970-2979.
[23]
Cui H, Mu Y, Yu L, et al. Methylation of the miR-126 gene associated with glioma progression[J]. Fam Cancer, 2016, 15(2): 317-324.
[24]
Hong C, Moorefield KS, Jun P, et al. Epigenome scans and cancer genome sequencing converge on WNK2, a kinase-independent suppressor of cell growth[J]. Proc Natl Acad Sci USA, 2007, 104(26): 10974-10979.
[25]
Alaminos M, Dávalos V, Ropero S, et al. EMP3, a myelin-related gene located in the critical 19q13.3 region, is epigenetically silenced and exhibits features of a candidate tumor suppressor in glioma and neuroblastoma[J]. Cancer Res, 2005, 65(7): 2565-2571.
[26]
Lindemann C, Hackmann O, Delic S, et al. SOCS3 promoter methylation is mutually exclusive to EGFR amplification in gliomas and promotes glioma cell invasion through STAT3 and FAK activation[J]. Acta Neuropathol, 2011, 122(2): 241-251.
[27]
Kurscheid S, Bady P, Sciuscio D, et al. Chromosome 7 gain and DNA hypermethylation at the HOXA10 locus are associated with expression of a stem cell related HOX-signature in glioblastoma[J]. Genome Biol, 2015, 16(1): 16.
[28]
Gömöri E, Pál J, Kovács B, et al. Concurrent hypermethylation of DNMT1, MGMT and EGFR genes in progression of gliomas[J]. Diagn Pathol, 2012, 7: 8.
[29]
Qi C, Lei L, Hu J, et al. Thrombospondin-1 is a prognostic biomarker and is correlated with tumor immune microenvironment in glioblastoma[J]. Oncol Lett, 2021, 21(1): 22.
[30]
Hesson LB, Cooper WN, Latif F. The role of RASSF1A methylation in cancer[J]. Dis Markers, 2007, 23(1-2): 73-87.
[31]
Liu L, Chen K, Wu J, et al. Downregulation of miR-452 promotes stem-like traits and tumorigenicity of gliomas[J]. Clin Cancer Res, 2013, 19(13): 3429-3438.
[32]
Fan K, Wang X, Zhang J, et al. Hypomethylation of CNTFRα is associated with proliferation and poor prognosis in lower grade gliomas[J]. Sci Rep, 2017, 7(1): 7079.
[33]
Chen J, Gong M, Lu S, et al. Detection of serum Alu element hypomethylation for the diagnosis and prognosis of glioma[J]. J Mol Neurosci, 2013, 50(2): 368-375.
[34]
Steponaitis G, Kazlauskas A, Vaitkienė P, et al. Oncosuppressive role of RUNX3 in human astrocytomas[J]. J Oncol, 2019, 2019: 1232434.
[35]
Dong X, Deng Q, Nie X, et al. Downregulation of HTATIP2 expression is associated with promoter methylation and poor prognosis in glioma[J]. Exp Mol Pathol, 2015, 98(2): 192-199.
[36]
Chu SH, Feng DF, Ma YB, et al. Promoter methylation and downregulation of SLC22A18 are associated with the development and progression of human glioma[J]. J Transl Med, 2011, 9: 156.
[37]
Kolodziej MA, Weischer C, Reinges MH, et al. NDRG2 and NDRG4 expression is altered in glioblastoma and influences survival in patients with MGMT-methylated tumors[J]. Anticancer Res, 2016, 36(3): 887-897.
[38]
Majchrzak-Celińska A, Sńocińska M, Barciszewska AM, et al. Wnt pathway antagonists, SFRP1, SFRP2, SOX17, and PPP2R2B, are methylated in gliomas and SFRP1 methylation predicts shorter survival[J]. J Appl Genet, 2016, 57(2): 189-197.
[39]
Delpu Y, Cordelier P, Cho WC, et al. DNA methylation and cancer diagnosis[J]. Int J Mol Sci, 2013, 14(7): 15029-15058.
[40]
Mendez FM, Núñez FJ, Garcia-Fabiani MB, et al. Epigenetic reprogramming and chromatin accessibility in pediatric diffuse intrinsic pontine gliomas: a neural developmental disease[J]. Neuro Oncol, 2020, 22(2): 195-206.
[41]
El-Hashash AHK. Histone H3K27M mutation in brain tumors[J]. Adv Exp Med Biol, 2021, 1283: 43-52.
[42]
Ganguly D, Sims M, Cai C, et al. Chromatin remodeling factor BRG1 regulates stemness and chemosensitivity of glioma initiating cells[J]. Stem Cells, 2018, 36(12): 1804-1815.
[43]
Masliah-Planchon J, Bièche I, Guinebretière JM, et al. SWI/SNF chromatin remodeling and human malignancies[J]. Annu Rev Pathol, 2015, 10: 145-171.
[44]
Yu L, Xu J, Liu J, et al. The novel chromatin architectural regulator SND1 promotes glioma proliferation and invasion and predicts the prognosis of patients[J]. Neuro Oncol, 2019, 21(6): 742-754.
[45]
Dong Z, Cui H. The emerging roles of RNA modifications in glioblastoma[J]. Cancers (Basel), 2020, 12(3): 736.
[46]
Zhang Y, Geng X, Li Q, et al. m6A modification in RNA: biogenesis, functions and roles in gliomas[J]. J Exp Clin Cancer Res, 2020, 39(1): 192.
[47]
Peng Z, Liu C, Wu M. New insights into long noncoding RNAs and their roles in glioma[J]. Mol Cancer, 2018, 17(1): 61.
[48]
Zhou K, Zhang C, Yao H, et al. Knockdown of long non-coding RNA NEAT1 inhibits glioma cell migration and invasion via modulation of SOX2 targeted by miR-132[J]. Mol Cancer, 2018, 17(1): 105.
[49]
Xiao Y, Zhu Z, Li J, et al. Expression and prognostic value of long non-coding RNA H19 in glioma via integrated bioinformatics analyses[J]. Aging (Albany NY), 2020, 12(4): 3407-3430.
[50]
Zhang D, Zhou H, Liu J, et al. Long noncoding RNA ASB16-AS1 promotes proliferation, migration, and invasion in glioma cells[J]. Biomed Res Int, 2019, 2019: 5437531.
[51]
Chai C, Song LJ, Han SY, et al. MicroRNA-21 promotes glioma cell proliferation and inhibits senescence and apoptosis by targeting SPRY1 via the PTEN/PI3K/AKT signaling pathway[J]. CNS Neurosci Ther, 2018, 24(5): 369-380.
[52]
Mohammad F, Weissmann S, Leblanc B, et al. EZH2 is a potential therapeutic target for H3K27M-mutant pediatric gliomas[J]. Nat Med, 2017, 23(4): 483-492.
[1] 王晗宇, 张司可, 张羽, 万欣, 贺秋霞, 李明明, 杨秀华. 超声造影在脑胶质瘤切除术术中的应用价值[J]. 中华医学超声杂志(电子版), 2023, 20(07): 755-760.
[2] 兰伟途, 武峰, 何建昌, 兰文达, 王万宏. miRNA-199a-5p靶向CDCA7L对胶质瘤细胞迁移及侵袭的影响[J]. 中华细胞与干细胞杂志(电子版), 2021, 11(05): 272-278.
[3] 徐新丽, 于小勇. 表观遗传——中医药治疗糖尿病肾病新视角[J]. 中华肾病研究电子杂志, 2022, 11(05): 276-280.
[4] 张瑞琪, 张丽娟, 孙斌. 甲状腺相关性眼病表观遗传学的研究进展[J]. 中华眼科医学杂志(电子版), 2023, 13(04): 226-230.
[5] 程亚飞, 任长远, 李海马, 孙恺, 马亚群. FSTL1基因在胶质瘤发展中作用的研究[J]. 中华神经创伤外科电子杂志, 2023, 09(04): 206-215.
[6] 王志文, 王长峰, 王海江. 肉桂醛经HIF-1α抑制肿瘤的研究进展及展望[J]. 中华神经创伤外科电子杂志, 2022, 08(04): 247-251.
[7] 余成龙, 刘静, 林帆, 张协军, 阳吉虎, 刘玉飞, 陈垒, 张玛莉, 蒋太鹏, 李维平, 黄国栋, 陈凡帆. 多学科诊疗门诊在神经肿瘤病例中的诊治效率评估[J]. 中华神经创伤外科电子杂志, 2022, 08(04): 229-235.
[8] 袁英淇, 闫润芝, 范益民. ATRX丢失与胶质瘤患者预后及IDH突变相关性的Meta分析[J]. 中华神经创伤外科电子杂志, 2022, 08(03): 161-167.
[9] 麦麦提力·米吉提, 李云雷, 吴昊, 李彦东, 沈宇晟, 吕明月, 朱国华. 弥散张量成像传导束重建技术指导高级别胶质瘤切除的临床研究[J]. 中华神经创伤外科电子杂志, 2022, 08(02): 101-105.
[10] 赵小玉, 李彦东, 吴昊, 范海, 吕明月, 沈宇晟, 盛成俊, 曾加, 吴徐超, 朱国华, 更·党木仁加甫. 外泌体miRNA在脑胶质瘤中的诊断、治疗和预后的研究进展[J]. 中华脑科疾病与康复杂志(电子版), 2021, 11(06): 370-374.
[11] 向琰, 黄国浩, 杨伟, 刘国龙, 谢源, 吕胜青. 显微镜下黄荧光引导技术切除高级别脑胶质瘤[J]. 中华脑科疾病与康复杂志(电子版), 2021, 11(05): 319-320.
[12] 冯海涛, 徐涛, 刘文阳, 孙晨, 曹尚超. 三维动脉自旋标记联合动态对比增强MRI对脑胶质瘤术后复发及放射性脑坏死诊断的研究[J]. 中华消化病与影像杂志(电子版), 2023, 13(04): 262-265.
[13] 张懿炜, 胡亚欣, 出良钊, 严昭, 曾茜, 蒲茜. CREB3通过下调FAK磷酸化水平抑制胶质瘤细胞增殖及侵袭转移的体外实验研究[J]. 中华临床医师杂志(电子版), 2023, 17(02): 202-209.
[14] 孔蕊, 姚群, 张小红, 吴晓博, 范颖. DNA甲基化检测在分流阴道镜检查中的应用[J]. 中华临床医师杂志(电子版), 2022, 16(01): 28-32.
[15] 黄贞亮, 赵铎. 针刀治疗胶质瘤术后头痛案[J]. 中华针灸电子杂志, 2022, 11(04): 144-145.
阅读次数
全文


摘要