表观遗传生物标志物在人类疾病早期诊治中的研究进展

doi:10.16288/j.yczz.17-220

遗传 ›› 2018, Vol. 40 ›› Issue (2): 104-115.doi: 10.16288/j.yczz.17-220

表观遗传生物标志物在人类疾病早期诊治中的研究进展

黎伟¹(),秦俊¹(),汪晖^2,³,陈廖斌^1,³

1. 武汉大学中南医院骨科，武汉 430071
2.武汉大学基础医学院药理学系，武汉 430071
3. 湖北省发育源性疾病重点实验室，武汉 430071

收稿日期:2017-10-16 修回日期:2018-01-03 出版日期:2018-02-20 发布日期:2018-01-22
作者简介:作者简介: 黎伟,硕士研究生,专业方向：骨关节病。E-mail: 444069914@qq.com|通讯作者: 秦俊,博士,主治医师,专业方向：骨关节病。E-mail: heart. blue@163.com
基金资助:
国家自然科学基金项目(81220108026,81401832)

Research progress of epigenetic biomarkers in the early diagnosis and treatment of human diseases

li Wei¹(),Qin Jun¹(),Wang Hui^2,³,Chen Liaobin^1,³

1. Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
2. Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China
3. Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China

Received:2017-10-16 Revised:2018-01-03 Online:2018-02-20 Published:2018-01-22
Supported by:
the National Natural Science Foundation of China(81220108026,81401832)

摘要/Abstract

摘要：

表观遗传修饰异常见于人类的多种疾病(如肿瘤、老年性疾病、发育源性疾病等),影响着这些疾病的发生发展。已有的研究表明,异常表观遗传改变可以作为疾病状态和疾病预测的生物标志物。表观遗传修饰改变的可逆性和可控性也为疾病早期的预防和治疗提供了新策略。本文对DNA甲基化修饰、组蛋白共价修饰、非编码RNA等三种表观遗传方式在肿瘤、老年性疾病和发育源性疾病的研究,以及三者作为表遗传生物标志物在疾病早期诊断和治疗的应用展开介绍,以期为肿瘤、老年性和发育源性相关疾病的诊断与治疗提供借鉴和参考。

关键词: 表观遗传修饰, 表遗传生物标志物, 肿瘤, 老年性疾病, 发育源性疾病

Abstract:

Abnormal epigenetic modifications are common in many diseases (such as tumors, senile and developmental diseases), and can influence the pathogenesis and progression of these diseases. Various studies demonstrated that abnormal epigenetic changes could be used as biomarkers for diagnosis of the disease status and prognosis of disease progression. The reversibility and controllability of epigenetic modifications also offer an opportunity to develop new strategies for the early prevention and treatment of diseases. In this review, we provide a brief overview of the latest discoveries in three areas of epigenetic research, i.e., DNA methylation, histone modifications and non-coding RNAs, and their potential applications in early diagnosis and treatment of tumors, senile and developmental diseases. We hope to provide some insights and references in developing strategies for the diagnosis and treatment of these diseases.

Key words: epigenetic modification, epigenetic biomarkers, tumors, senile diseases, developmental diseases

黎伟, 秦俊, 汪晖, 陈廖斌. 表观遗传生物标志物在人类疾病早期诊治中的研究进展[J]. 遗传, 2018, 40(2): 104-115.

li Wei, Qin Jun, Wang Hui, Chen Liaobin. Research progress of epigenetic biomarkers in the early diagnosis and treatment of human diseases[J]. Hereditas(Beijing), 2018, 40(2): 104-115.

参考文献

[1]	Prins GS, Ye SH, Birch L, Zhang X, Cheong A, Lin H, Calderon-Gierszal E, Groen J, Hu WY, Ho SM, Van Breemen RB . Prostate cancer risk and DNA methylation signatures in aging rats following developmental BPA Exposure: a dose-response analysis. Environ Health Perspect, 2017, 125(7):077007.
[2]	Graca I, Pereira-Silva E, Henrique R, Packham G, Crabb SJ, Jeronimo C . Epigenetic modulators as therapeutic targets in prostate cancer. Clin Epigenetics, 2016, 8(1):98.
[3]	Tahara T, Tahara S, Horiguchi N, Kawamura T, Okubo M, Yamada H, Yoshida D, Ohmori T, Maeda K, Komura N, Ikuno H, Jodai Y, Kamano T, Nagasaka M, Nakagawa Y, Tsukamoto T, Urano M, Shibata T, Kuroda M, Ohmiya N . Methylation status of IGF2 DMR and LINE1 in leukocyte DNA provides distinct clinicopathological features of gastric cancer patients. Clin Exp Med, 2017. DOI: 10.1007/s10238-017-0471-4.
[4]	Moruzzi S, Guarini P, Udali S, Ruzzenente A, Guglielmi A, Conci S, Pattini P, Martinelli N, Olivieri O, Tammen S A, Choi S W, Friso S . One-carbon genetic variants and the role of MTHFD1 1958G>A in liver and colon cancer risk according to global DNA methylation. PLoS One, 2017, 12(10):e0185792.
[5]	Iwata A, Nagata K, Hatsuta H, Takuma H, Bundo M, Iwamoto K, Tamaoka A, Murayama S, Saido T, Tsuji S . Altered CpG methylation in sporadic Alzheimer's disease is associated with APP and MAPT dysregulation. Hum Mol Genet, 2014, 23(3):648-656.
[6]	Lee J, Hagerty S, Cormier KA, Kim J, Kung AL, Ferrante RJ, Ryu H . Monoallele deletion of CBP leads to pericentromeric heterochromatin condensation through ESET expression and histone H3(K9) methylation. Hum Mol Genet, 2008, 17(12):1774-1782.
[7]	Begum G, Davies A, Stevens A, Oliver M, Jaquiery A, Challis J, Harding J, Bloomfield F, White A . Maternal undernutrition programs tissue-specific epigenetic changes in the glucocorticoid receptor in adult offspring. Endocrinology, 2013, 154(12):4560-4569.
[8]	Baserga M, Kaur R, Hale MA, Bares A, Yu X, Callaway CW , McKnight RA, Lane RH. Fetal growth restriction alters transcription factor binding and epigenetic mechanisms of renal 11β-hydroxysteroid dehydrogenase type 2 in a sex-specific manner. Am J Physiol Regul Integr Comp Physiol, 2010, 299(1):R334-R342.
[9]	Baserga M, Hale MA, Wang ZM , YuX, Callaway CW, McKnight RA, Lane RH. Uteroplacental insufficiency alters nephrogenesis and downregulates cyclooxygenase-2 expression in a model of IUGR with adult-onset hypertension. Am J Physiol Regul Integr Comp Physiol, 2007, 292(5):R1943-R1955.
[10]	Masuyama H, Hiramatsu Y . Effects of a high-fat diet exposure in utero on the metabolic syndrome-like phenomenon in mouse offspring through epigenetic changes in adipocytokine gene expression. Endocrinology, 2012, 153(6):2823-2830.
[11]	Li D, Tian YJ, Guo J, Sun WP, Lun YZ, Guo M, Luo N, Cao Y, Cao JM, Gong XJ, Zhou SS . Nicotinamide supplementation induces detrimental metabolic and epigenetic changes in developing rats. Br J Nutr, 2013, 110(12):2156-2164.
[12]	Kandimalla R, Van Tilborg AA, Zwarthoff EC . DNA methylation-based biomarkers in bladder cancer. Nat Rev Urol, 2013, 10(6):327-335.
[13]	Besaratinia A, Cockburn M, Tommasi S . Alterations of DNA methylome in human bladder cancer. Epigenetics, 2013, 8(10):1013-1022.
[14]	Pasinetti GM, Ho L, Dooley C, Abbi B, Lange G . Select non-coding RNA in blood components provide novel clinically accessible biological surrogates for improved identification of traumatic brain injury in OEF/OIF Veterans. Am J Neurodegener Dis, 2012, 1(1):88-98.
[15]	Godfrey KM, Sheppard A, Gluckman PD, Lillycrop KA, Burdge GC , McLean C, Rodford J, Slater-Jefferies JL, Garratt E, Crozier SR, Emerald BS, Gale CR, Inskip HM, Cooper C, Hanson MA. Epigenetic gene promoter methylation at birth is associated with child's later adiposity. Diabetes, 2011, 60(5):1528-1534.
[16]	Jin BL, Robertson KD. DNA methyltransferases, DNA damage repair, and cancer. In: Karpf A. Epigenetic Alterations in Oncogenesis. Advances in Experimental Medicine and Biology. New York, NY: Springer, 2013, 754:3-29.
[17]	Castillo-Aguilera O, Depreux P, Halby L, Arimondo PB, Goossens L . DNA Methylation Targeting: The DNMT/ HMT Crosstalk Challenge. Biomolecules, 2017, 7(1):E3.
[18]	Jeltsch A, Jurkowska RZ . Allosteric control of mammalian DNA methyltransferases - a new regulatory paradigm. Nucleic Acids Res, 2016, 44(18):8556-8575.
[19]	Miranda TB, Jones PA . DNA methylation: the nuts and bolts of repression. J Cell Physiol, 2007, 213(2):384-390.
[20]	Bird A . Perceptions of epigenetics. Nature, 2007, 447(7143):396-398.
[21]	Chrun ES, Modolo F, Daniel FI . Histone modifications: A review about the presence of this epigenetic phenomenon in carcinogenesis. Pathol Res Pract, 2017, 213(11):1329-1339.
[22]	Greer EL, Shi Y . Histone methylation: a dynamic mark in health, disease and inheritance. Nat Rev Genet, 2012, 13(5):343-357.
[23]	Cardin S, Guasch E, Luo XB, Naud P, Le Quang K, Shi YF, Tardif JC, Comtois P, Nattel S . Role for MicroRNA-21 in atrial profibrillatory fibrotic remodeling associated with experimental postinfarction heart failure. Circ Arrhythm Electrophysiol, 2012, 5(5):1027-1035.
[24]	Bartel DP . MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 2004, 116(2):281-297.
[25]	Molotski N, Soen Y . Differential association of microRNAs with polysomes reflects distinct strengths of interactions with their mRNA targets. RNA, 2012, 18(9):1612-1623.
[26]	Bentwich I, Avniel A, Karov Y, Aharonov R, Gilad S, Barad O, Barzilai A, Einat P, Einav U, Meiri E, Sharon E, Spector Y, Bentwich Z . Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet, 2005, 37(7):766-770.
[27]	Fatica A, Bozzoni I . Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet, 2014, 15(1):7-21.
[28]	Batista PJ, Chang HY . Long noncoding RNAs: cellular address codes in development and disease. Cell, 2013, 152(6):1298-1307.
[29]	Yu C, Li L, Xie F, Guo S, Liu F, Dong N, Wang Y . LncRNA TUG1 sponges miR-204-5p to promote osteoblast differentiation through upregulating Runx2 in aortic valve calcification. Cardiovasc Res, 2017, 114(1):168-179.
[30]	Flynn RA, Chang HY . Long noncoding RNAs in cell-fate programming and reprogramming. Cell Stem Cell, 2014, 14(6):752-761.
[31]	Siebenk?s C, Chiappinelli KB, Guzzetta AA, Sharma A, Jeschke J, Vatapalli R, Baylin SB, Ahuja N . Inhibiting DNA methylation activates cancer testis antigens and expression of the antigen processing and presentation machinery in colon and ovarian cancer cells. PLoS One, 2017, 12(6):e0179501.
[32]	Lam K, Pan K, Linnekamp JF, Medema JP, Kandimalla R . DNA methylation based biomarkers in colorectal cancer: A systematic review. Biochim Biophys Acta: Rev Cancer, 2016, 1866(1):106-120.
[33]	Yang B, Guo MZ, Herman JG, Clark DP . Aberrant promoter methylation profiles of tumor suppressor genes in hepatocellular carcinoma. Am J Pathol, 2003, 163(3):1101-1107.
[34]	Xing XB, Cai WB, Luo L, Liu LS, Shi HJ, Chen MH . The prognostic value of p16 hypermethylation in cancer: a meta-analysis. PLoS One, 2013, 8(6):e66587.
[35]	Quintás-Cardama A, Kantarjian H, Estrov Z, Borthakur G, Cortes J, Verstovsek S . Therapy with the histone deacetylase inhibitor pracinostat for patients with myelofibrosis. Leuk Res, 2012, 36(9):1124-1127.
[36]	Liu LH, Ling XX, Liang HR, Gao YT, Yang H, Shao JL, Tang HW . Hypomethylation mediated by decreased DNMTs involves in the activation of proto-oncogene MPL in TK6 cells treated with hydroquinone. Toxicol Lett, 2012, 209(3):239-245.
[37]	Ehrlich M, Lacey M. DNA hypomethylation and hemimethylation in cancer. In: Karpf A, ed. Epigenetic Alterations in Oncogenesis. Advances in Experimental Medicine and Biology. New York, NY: Springer, 2013, 754:31-56.
[38]	Maleszewska M, Kaminska B . Deregulation of histone- modifying enzymes and chromatin structure modifiers contributes to glioma development. Future Oncol, 2015, 11(18):2587-2601.
[39]	Park E, Kim Y, Ryu H, Kowall NW, Lee J, Ryu H . Epigenetic mechanisms of Rubinstein-Taybi syndrome. Neuromol Med, 2014, 16(1):16-24.
[40]	Okugawa Y, Grady WM , Goel A. Epigenetic alterations in colorectal cancer: emerging biomarkers. Gastroenterology, 2015, 149(5):1204-1225.e12.
[41]	Esteller M . Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet, 2007, 8(4):286-298.
[42]	Yao JY, Zhang L, Zhang X, He ZY, Ma Y, Hui LJ, Wang X, Hu YP . H3K27 trimethylation is an early epigenetic event of p16 INK4a silencing for regaining tumorigenesis in fusion reprogrammed hepatoma cells. J Biol Chem, 2010, 285(24):18828-18837.
[43]	Fraga MF, Ballestar E, Villar-Garea A, Boix-Chornet M, Espada J, Schotta G, Bonaldi T, Haydon C, Ropero S, Petrie K, Iyer NG, Pérez-Rosado A, Calvo E, Lopez JA, Cano A, Calasanz MJ, Colomer D, Piris MA, Ahn N, Imhof A, Caldas C, Jenuwein T, Esteller M . Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet, 2005, 37(4):391-400.
[44]	Hu WL , Gao A . The role of long non-coding RNAs in hematologic malignancies. Hereditas (Beijing), 2015, 37( 11): 1095- 1104.
[44]	胡婉莉, 高艾 . 长链非编码RNA在血液系统肿瘤中作用的研究进展. 遗传, 2015, 37( 11): 1095- 1104. [DOI]
[45]	Wang J, Yang H, Si Y, Hu D, Yu Y, Zhang Y, Gao M, Zhang H . Iodine Promotes Tumorigenesis of Thyroid Cancer by Suppressing Mir-422a and Up-Regulating MAPK1. Cell Physiol Biochem, 2017, 43(4):1325-1336.
[46]	Da Silva Oliveira KC, Araújo TMT, Albuquerque CI, Barata GA, Gigek CO, Leal MF, Wisnieski F, Rodrigues Mello Junior FA, Khayat AS, De Assumpcao PP, Rodriguez Burbano RM, Smith MC, Calcagno DQ . Role of miRNAs and their potential to be useful as diagnostic and prognostic biomarkers in gastric cancer. World J Gastroenterol, 2016, 22(35):7951-7962.
[47]	Xia JZ, Guo XQ, Yan J, Deng KY . The role of miR-148a in gastric cancer. J Cancer Res Clin Oncol, 2014, 140(9):1451-1456.
[48]	Wang Y, Sun BS, Sun HZ, Zhao XL, Wang XD, Zhao N, Zhang YH, Li YL, Gu Q, Liu F, Shao B, An JD . Regulation of proliferation, angiogenesis and apoptosis in hepatocellular carcinoma by miR-26b-5p. Tumour Biol, 2016, 37(8):10965-10979.
[49]	Smith A L, Robin T P, Ford H L . Molecular pathways: targeting the TGF-beta pathway for cancer therapy. Clin Cancer Res, 2012, 18(17):4514-4521.
[50]	Mastroeni D , McKee A, Grover A, Rogers J, Coleman PD. Epigenetic differences in cortical neurons from a pair of monozygotic twins discordant for Alzheimer's disease. PLoS One, 2009, 4(8):e6617.
[51]	Loeser RF, Im HJ, Richardson B, Lu Q, Chubinskaya S . Methylation of the OP-1 promoter: potential role in the age-related decline in OP-1 expression in cartilage. Osteoart Cartil, 2009, 17(4):513-517.
[52]	Silva PNO, Gigek CO, Leal MF, Bertolucci PH, De Labio RW, Pay?o SLM, Smith MAC . Promoter methylation analysis of SIRT3, SMARCA5, HTERT and CDH1 genes in aging and Alzheimer's disease. J Alzheimers Dis, 2008, 13(2):173-176.
[53]	Wood H . Neurodegenerative disease: altered DNA methylation and RNA splicing could be key mechanisms in Huntington disease. Nat Rev Neurol, 2013, 9(3):119.
[54]	Wang CM, Tsai SN, Yew TW, Kwan YW, Ngai SM . Identification of histone methylation multiplicities patterns in the brain of senescence-accelerated prone mouse 8. Biogerontology, 2010, 11(1):87-102.
[55]	Zhang KL, Schrag M, Crofton A, Trivedi R, Vinters H, Kirsch W . Targeted proteomics for quantification of histone acetylation in Alzheimer's disease. Proteomics, 2012, 12(8):1261-1268.
[56]	Quinti L, Chopra V, Rotili D, Valente S, Amore A, Franci G, Meade S, Valenza M, Altucci L, Maxwell MM, Cattaneo E, Hersch S, Mai A, Kazantsev A. Evaluation of histone deacetylases as drug targets in Huntington's disease models. Study of HDACs in brain tissues from R6/2 and CAG140 knock-in HD mouse models and human patients and in a neuronal HD cell model. PLoS Curr, 2010, 2: RRN1172.
[57]	Sonntag KC . MicroRNAs and deregulated gene expression networks in neurodegeneration. Brain Res, 2010, 1338:48-57.
[58]	Geekiyanage H, Chan C . MicroRNA-137/181c regulates serine palmitoyltransferase and in turn amyloid β, novel targets in sporadic Alzheimer's disease. J Neurosci, 2011, 31(41):14820-14830.
[59]	Roberts TC, Morris KV, Wood MJA . The role of long non-coding RNAs in neurodevelopment, brain function and neurological disease. Philosoph Transact Royal Soc B-Biolog Sci, 2014, 369(1652):20130507.
[60]	Ho SM, Tang WY . Techniques used in studies of epigenome dysregulation due to aberrant DNA methylation: an emphasis on fetal-based adult diseases. Reprod Toxicol, 2007, 23(3):267-282.
[61]	Ganu RS, Harris RA, Collins K, Aagaard KM . Early origins of adult disease: approaches for investigating the programmable epigenome in humans, nonhuman primates, and rodents. ILAR J, 2012, 53(3-4):306-321.
[62]	Simmons R . Developmental origins of adult metabolic disease. Endocrinol Metab Clin North Am, 2006, 35(1):193-204.
[63]	Xu JW, He G, Zhu JD, Zhou XY, St Clair D, Wang T, Xiang YQ, Zhao QZ, Xing QH, Liu Y, Wang L, Li Q, He L, Zhao XZ. Prenatal nutritional deficiency reprogrammed postnatal gene expression in mammal brains: implications for schizophrenia. Int J Neuropsychopharmacol, 2014, 18(4):pyu054.
[64]	Wang ZP, Xu L, Zhu XP, Cui WG, Sun Y, Nishijo H, Peng YW, Li RX . Demethylation of specific Wnt/β- catenin pathway genes and its upregulation in rat brain induced by prenatal valproate exposure. Anatom Record, 2010, 293(11):1947-1953.
[65]	Lee HS . Impact of maternal diet on the epigenome during In Utero Life and the developmental programming of diseases in childhood and adulthood. Nutrients, 2015, 7(11):9492-9507.
[66]	Begum G, Stevens A, Smith EB, Connor K, Challis JR, Bloomfield F, White A . Epigenetic changes in fetal hypothalamic energy regulating pathways are associated with maternal undernutrition and twinning. FASEB J, 2012, 26(4):1694-1703.
[67]	Einstein F, Thompson RF, Bhagat TD, Fazzari MJ, Verma A, Barzilai N, Greally JM . Cytosine methylation dysregulation in neonates following intrauterine growth restriction. PLoS One, 2010, 5(1):e8887.BACKGROUND:Perturbations of the intrauterine environment can affect fetal development during critical periods of plasticity, and can increase susceptibility to a number of age-related diseases (e.g., type 2 diabetes mellitus; T2DM), manifesting as late as decades later. We hypothesized that this biological memory is mediated by permanent alterations of the epigenome in stem cell populations, and focused our studies specifically on DNA methylation in CD34+ hematopoietic stem and progenitor cells from cord blood from neonates with intrauterine growth restriction (IUGR) and control subjects.METHODS AND FINDINGS:Our epigenomic assays utilized a two-stage design involving genome-wide discovery followed by quantitative, single-locus validation. We found that changes in cytosine methylation occur in response to IUGR of moderate degree and involving a restricted number of loci. We also identify specific loci that are targeted for dysregulation of DNA methylation, in particular the hepatocyte nuclear factor 4alpha (HNF4A) gene, a well-known diabetes candidate gene not previously associated with growth restriction in utero, and other loci encoding HNF4A-interacting proteins.CONCLUSIONS:Our results give insights into the potential contribution of epigenomic dysregulation in mediating the long-term consequences of IUGR, and demonstrate the value of this approach to studies of the fetal origin of adult disease.
[68]	Inadera H . Developmental origins of obesity and type 2 diabetes: molecular aspects and role of chemicals. Environ Health Prev Med, 2013, 18(3):185-197.
[69]	Tsukuda K, Mogi M, Iwanami J, Min LJ, Jing F, Ohshima K, Horiuchi M . Influence of angiotensin II type 1 receptor-associated protein on prenatal development and adult hypertension after maternal dietary protein restriction during pregnancy. J Am Soc Hypertens, 2012, 6(5):324-330.
[70]	Li ZX, Huang HF . Epigenetic abnormality: a possible mechanism underlying the fetal origin of polycystic ovary syndrome. Med Hypoth, 2008, 70(3):638-642.
[71]	Pinney SE, Santos LJJ, Han Y, Stoffers DA, Simmons RA . Exendin-4 increases histone acetylase activity and reverses epigenetic modifications that silence Pdx1 in the intrauterine growth retarded rat. Diabetologia, 2011, 54(10):2606-2614.
[72]	Park JH, Stoffers DA, Nicholls RD, Simmons RA . Development of type 2 diabetes following intrauterine growth retardation in rats is associated with progressive epigenetic silencing of Pdx1. J Clin Invest, 2008, 118(6):2316-2324.
[73]	Yang BT, Dayeh TA, Volkov PA, Kirkpatrick CL, Malmgren S, Jing XJ, Renstr?m E, Wollheim C B, Nitert M D, Ling C . Increased DNA methylation and decreased expression of PDX-1 in pancreatic islets from patients with type 2 diabetes. Mol Endocrinol, 2012, 26(7):1203-1212.
[74]	Li MT , Cao LL , Yang Y . The role of epigenetic modification in glucose and lipid metabolism. Hereditas (Beijing), 2014, 36( 3): 200- 207.
[74]	李美婷, 曹林林, 杨洋 . 表观遗传修饰在糖脂代谢中的作用. 遗传, 2014, 36( 3): 200- 207.
[75]	Painter RC, De Rooij SR, Hutten BA, Bossuyt PMM, De Groot E, Osmond C, Barker DJP, Bleker OP, Roseboom TJ . Reduced intima media thickness in adults after prenatal exposure to the Dutch famine. Atherosclerosis, 2007, 193(2):421-427.
[76]	Suter M, Bocock P, Showalter L, Hu M, Shope C , McKnight R, Grove K, Lane R, Aagaard-Tillery K. Epigenomics: maternal high-fat diet exposure in utero disrupts peripheral circadian gene expression in nonhuman primates. FASEB J, 2011, 25(2):714-726.
[77]	Xu XF, Lv Y, Gu WZ, Tang LL, Wei JK, Zhang LY, Du LZ . Epigenetics of hypoxic pulmonary arterial hypertension following intrauterine growth retardation rat: epigenetics in PAH following IUGR. Respir Res, 2013, 14(1):20.
[78]	Chakraborty C, Doss CG, Bandyopadhyay S, Agoramoorthy G . Influence of miRNA in insulin signaling pathway and insulin resistance: micro-molecules with a major role in type-2 diabetes. Wiley Interdiscip Rev RNA, 2014, 5(5):697-712.
[79]	Sandoval J, Peiró-Chova L, Pallardó FV, García- Gimenez JL . Epigenetic biomarkers in laboratory diagnostics: emerging approaches and opportunities. Expert Rev Mol Diagn, 2013, 13(5):457-471.
[80]	Mehta A, Dobersch S, Romero-Olmedo AJ, Barreto G . Epigenetics in lung cancer diagnosis and therapy. Cancer Metast Rev, 2015, 34(2):229-241.
[81]	Coyle YM, Xie XJ, Lewis CM, Bu DW, Milchgrub S, Euhus DM . Role of physical activity in modulating breast cancer risk as defined by APC and RASSF1A promoter hypermethylation in nonmalignant breast tissue. Cancer Epidemiol Biomarkers Prev, 2007, 16(2):192-196.
[82]	Salehi R, Atapour N, Vatandoust N, Farahani N, Ahangari F, Salehi AR . Methylation pattern of ALX4 gene promoter as a potential biomarker for blood-based early detection of colorectal cancer. Adv Biomed Res, 2015, 4(1):252.
[83]	Lee BB, Lee EJ, Jung EH, Chun HK, Chang DK, Song SY, Park J, Kim DH . Aberrant methylation of APC, MGMT, RASSF2A, and Wif-1 genes in plasma as a biomarker for early detection of colorectal cancer. Clin Cancer Res, 2009, 15(19):6185-6191.
[84]	Gu JD, Wen YJ, Zhu SW, Hua F, Zhao H, Xu HR, You JC, Sun LL, Wang WQ, Chen J, Zhou QH . Association between P 16INK4a promoter methylation and non-small cell lung cancer: a meta-analysis. PLoS One , 2013, 8(4):e60107.
[85]	Seligson DB, Horvath S , McBrian MA, Mah V, Yu H, Tze S, Wang Q, Chia D, Goodglick L, Kurdistani SK. Global levels of histone modifications predict prognosis in different cancers. Am J Pathol, 2009, 174(5):1619-1628.
[86]	Rodríguez-Paredes M, Esteller M . Cancer epigenetics reaches mainstream oncology. Nat Med, 2011, 17(3):330-339.
[87]	Son CH, Lee HR, Koh EK, Shin DY, Bae JH, Yang K, Park YS . Combination treatment with decitabine and ionizing radiation enhances tumor cells susceptibility of T cells. Sci Rep, 2016, 6:32470.
[88]	Plumb JA, Strathdee G, Sludden J, Kaye SB, Brown R . Reversal of drug resistance in human tumor xenografts by 2'-deoxy-5-azacytidine-induced demethylation of the hMLH1 gene promoter. Cancer Res, 2000, 60(21):6039-6044.
[89]	Chiu HW, Yeh YL, Wang YC, Huang WJ, Ho SY, Lin PP, Wang YJ . Combination of the novel histone deacetylase inhibitor YCW1 and radiation induces autophagic cell death through the downregulation of BNIP3 in triple- negative breast cancer cells in vitro and in an orthotopic mouse model. Mol Cancer, 2016, 15(1):46.
[90]	Horvath S, Zhang YF, Langfelder P, Kahn RS, Boks MP, Van Eijk K , Van Den Berg LH, Ophoff RA. Aging effects on DNA methylation modules in human brain and blood tissue. Genome Biol, 2012, 13(10):R97.
[91]	Cacciapuoti F . Lowering homocysteine levels with folic acid and B-vitamins do not reduce early atherosclerosis, but could interfere with cognitive decline and Alzheimer's disease. J Thromb Thrombol, 2013, 36(3):258-262.
[92]	Nicholas AP, Lubin FD, Hallett PJ, Vattem P, Ravenscroft P, Bezard E, Zhou SB, Fox SH, Brotchie JM, Sweatt JD, Standaert DG . Striatal histone modifications in models of levodopa-induced dyskinesia. J Neurochem, 2008, 106(1):486-494.
[93]	Wang J, Yu JT, Tan MS, Jiang T, Tan L . Epigenetic mechanisms in Alzheimer's disease: implications for pathogenesis and therapy. Ageing Res Rev, 2013, 12(4):1024-1041.
[94]	Poon LLM, Leung TN, Lau TK, Chow KCK, Lo Dennis YM . Differential DNA methylation between fetus and mother as a strategy for detecting fetal DNA in maternal plasma. Clin Chem, 2002, 48(1):35-41.
[95]	Tsui DWY, Chiu RWK, Lo Dennis YM . Epigenetic approaches for the detection of fetal DNA in maternal plasma. Chimerism, 2010, 1(1):30-35.
[96]	Liu FL , Zhou J , Zhang W , Wang H . Epigenetic regulation and related diseases during placental development. Hereditas (Beijing), 2017, 39( 4): 263- 275.
[96]	刘福林, 周瑾, 张蔚, 汪晖 . 胎盘发育过程中的表观遗传学改变及其相关疾病. 遗传, 2017, 39( 4): 263- 275.
[97]	Perkins E, Murphy SK, Murtha AP, Schildkraut J, Jirtle RL, Demark-Wahnefried W, Forman MR, Kurtzberg J, Overcash F, Huang Z, Hoyo C . Insulin-like growth factor 2/H19 methylation at birth and risk of overweight and obesity in children. J Pediatr, 2012, 161(1):31-39.
[98]	Heo HJ, Tozour JN, Delahaye F, Zhao YM, Cui LG, Barzilai N, Einstein FH . Advanced aging phenotype is revealed by epigenetic modifications in rat liver afterin utero malnutrition. Aging Cell, 2016, 15(5):964-972.
[99]	Ma BS, Wilker EH, Willis-Owen SA, Byun HM, Wong KCC, Motta V, Baccarelli AA, Schwartz J, Cookson WOCM, Khabbaz K, Mittleman MA, Moffatt MF, Liang LM . Predicting DNA methylation level across human tissues. Nucleic Acids Res, 2014, 42(6):3515-3528.
[100]	Davies MN, Volta M, Pidsley R, Lunnon K, Dixit A, Lovestone S, Coarfa C, Harris RA, Milosavljevic A, Troakes C, Al-Sarraj S, Dobson R, Schalkwyk LC, Mill J . Functional annotation of the human brain methylome identifies tissue-specific epigenetic variation across brain and blood. Genome Biol, 2012, 13(6):R43.
[101]	Kehler L, Biro O, Lazar L, Rigo J, Nagy B . Elevated hsa-miR-99a levels in maternal plasma may indicate congenital heart defects. Biomed Rep, 2015, 3(6):869-873.
[102]	Weaver ICG, Cervoni N, Champagne F A , D'Alessio AC, Sharma S, Seckl JR, Dymov S, Szyf M, Meaney MJ. Epigenetic programming by maternal behavior. Nat Neurosci, 2004, 7(8):847-854.
[103]	Ke X, Schober ME , McKnight RA, O'Grady S, Caprau D, Yu X, Callaway CW, Lane RH. Intrauterine growth retardation affects expression and epigenetic characteristics of the rat hippocampal glucocorticoid receptor gene. Physiol Genomics, 2010, 42(2):177-189.
[104]	Lillycrop KA, Phillips ES, Jackson AA, Hanson MA, Burdge GC . Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring. J Nutr, 2005, 135(6):1382-1386.
[105]	Gluckman PD, Lillycrop KA, Vickers MH, Pleasants AB, Phillips ES, Beedle AS, Burdge GC, Hanson MA . Metabolic plasticity during mammalian development is directionally dependent on early nutritional status. Proc Natl Acad Sci USA, 2007, 104(31):12796-12800.
[106]	Marmorstein R, Roth SY . Histone acetyltransferases: function, structure, and catalysis. Curr Opin Genet Dev, 2001, 11(2):155-161.
[107]	Zhao L, Chen CN, Hajji N, Oliver E, Cotroneo E, Wharton J, Wang DR, Li M , McKinsey TA, Stenmark KR, Wilkins MR. Histone deacetylation inhibition in pulmonary hypertension: therapeutic potential of valproic acid and suberoylanilide hydroxamic acid. Circulation, 2012, 126(4):455-467.
[108]	Kim B, Hong J . An overview of naturally occurring histone deacetylase inhibitors. Curr Top Med Chem, 2015, 14(24):2759-2782.
[109]	Tan S, Liu ZP . Natural products as zinc-dependent histone deacetylase inhibitors. ChemMedChem, 2015, 10(3):441-450.

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表观遗传生物标志物在人类疾病早期诊治中的研究进展

Research progress of epigenetic biomarkers in the early diagnosis and treatment of human diseases

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