CLC number: R541.9
On-line Access: 2024-08-27
Received: 2023-10-17
Revision Accepted: 2024-05-08
Crosschecked: 2020-06-05
Cited: 0
Clicked: 3542
Kun Zhao, Chuan-xi Yang, Peng Li, Wei Sun, Xiang-qing Kong. Epigenetic role of N6-methyladenosine (m6A) RNA methylation in the cardiovascular system[J]. Journal of Zhejiang University Science B, 2020, 21(7): 509-523.
@article{title="Epigenetic role of N6-methyladenosine (m6A) RNA methylation in the cardiovascular system",
author="Kun Zhao, Chuan-xi Yang, Peng Li, Wei Sun, Xiang-qing Kong",
journal="Journal of Zhejiang University Science B",
volume="21",
number="7",
pages="509-523",
year="2020",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1900680"
}
%0 Journal Article
%T Epigenetic role of N6-methyladenosine (m6A) RNA methylation in the cardiovascular system
%A Kun Zhao
%A Chuan-xi Yang
%A Peng Li
%A Wei Sun
%A Xiang-qing Kong
%J Journal of Zhejiang University SCIENCE B
%V 21
%N 7
%P 509-523
%@ 1673-1581
%D 2020
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1900680
TY - JOUR
T1 - Epigenetic role of N6-methyladenosine (m6A) RNA methylation in the cardiovascular system
A1 - Kun Zhao
A1 - Chuan-xi Yang
A1 - Peng Li
A1 - Wei Sun
A1 - Xiang-qing Kong
J0 - Journal of Zhejiang University Science B
VL - 21
IS - 7
SP - 509
EP - 523
%@ 1673-1581
Y1 - 2020
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1900680
Abstract: As the most prevalent and abundant transcriptional modification in the eukaryotic genome, the continuous and dynamic regulation of N6-methyladenosine (m6A) has been shown to play a vital role in physiological and pathological processes of cardiovascular diseases (CVDs), such as ischemic heart failure (HF), myocardial hypertrophy, myocardial infarction (MI), and cardiomyogenesis. Regulation is achieved by modulating the expression of m6A enzymes and their downstream cardiac genes. In addition, this process has a major impact on different aspects of internal biological metabolism and several other external environmental effects associated with the development of CVDs. However, the exact molecular mechanism of m6A epigenetic regulation has not been fully elucidated. In this review, we outline recent advances and discuss potential therapeutic strategies for managing m6A in relation to several common CVD-related metabolic disorders and external environmental factors. Note that an appropriate understanding of the biological function of m6A in the cardiovascular system will pave the way towards exploring the mechanisms responsible for the development of other CVDs and their associated symptoms. Finally, it can provide new insights for the development of novel therapeutic agents for use in clinical practice.
[1]Abdul-Ghani MA, Jayyousi A, Defronzo RA, et al., 2019. Insulin resistance the link between T2DM and CVD: basic mechanisms and clinical implications. Curr Vasc Pharmacol, 17(2):153-163.
[2]Asher G, Gatfield D, Stratmann M, et al., 2008. Sirt1 regulates circadian clock gene expression through PER2 deacetylation. Cell, 134(2):317-328.
[3]Bartosovic M, Molares HC, Gregorova P, et al., 2017. N6-methyladenosine demethylase FTO targets pre-mRNAs and regulates alternative splicing and 3'-end processing. Nucleic Acids Res, 45(19):11356-11370.
[4]Bayarsaihan D, 2011. Epigenetic mechanisms in inflammation. J Dent Res, 90(1):9-17.
[5]Bochmann L, Sarathchandra P, Mori F, et al., 2010. Revealing new mouse epicardial cell markers through transcriptomics. PLoS ONE, 5(6):e11429.
[6]Boissel S, Reish O, Proulx K, et al., 2009. Loss-of-function mutation in the dioxygenase-encoding FTO gene causes severe growth retardation and multiple malformations. Am J Hum Genet, 85(1):106-111.
[7]Buysschaert I, Schmidt T, Roncal C, et al., 2008. Genetics, epigenetics and pharmaco-(epi)genomics in angiogenesis. J Cell Mol Med, 12(6b):2533-2551.
[8]Cai CL, Martin JC, Sun YF, et al., 2008. A myocardial lineage derives from Tbx18 epicardial cells. Nature, 454(7200):104-108.
[9]Cai M, Liu Q, Jiang Q, et al., 2019. Loss of m6A on FAM134B promotes adipogenesis in porcine adipocytes through m6A-YTHDF2-dependent way. IUBMB Life, 71(5):580-586.
[10]Calvanese V, Fraga MF, 2012. Epigenetics of embryonic stem cells. Adv Exp Med Biol, 741:231-253.
[11]Carnevali L, Graiani G, Rossi S, et al., 2014. Signs of cardiac autonomic imbalance and proarrhythmic remodeling in FTO deficient mice. PLoS ONE, 9(4):e95499.
[12]Cecil JE, Tavendale R, Watt P, et al., 2008. An obesity-associated FTO gene variant and increased energy intake in children. N Engl J Med, 359(24):2558-2566.
[13]Chen JL, Du B, 2019. Novel positioning from obesity to cancer: FTO, an m6A RNA demethylase, regulates tumour progression. J Cancer Res Clin Oncol, 145(1):19-29.
[14]Cheng H, Xuan HW, Green CD, et al., 2018. Repression of human and mouse brain inflammaging transcriptome by broad gene-body histone hyperacetylation. Proc Natl Acad Sci USA, 115(29):7611-7616.
[15]Church C, Moir L, McMurray F, et al., 2010. Overexpression of Fto leads to increased food intake and results in obesity. Nat Genet, 42(12):1086-1092.
[16]Cole MA, Jamil AHA, Heather LC, et al., 2016. On the pivotal role of PPARα in adaptation of the heart to hypoxia and why fat in the diet increases hypoxic injury. FASEB J, 30(8):2684-2697.
[17]Cosselman KE, Navas-Acien A, Kaufman JD, 2015. Environmental factors in cardiovascular disease. Nat Rev Cardiol, 12(11):627-642.
[18]da Luz Sousa Fialho M, Jamil AHA, Stannard GA, et al., 2019. Hypoxia-inducible factor 1 signalling, metabolism and its therapeutic potential in cardiovascular disease. Biochim Biophys Acta Mol Basis Dis, 1865(4):831-843.
[19]Dang CV, Semenza GL, 1999. Oncogenic alterations of metabolism. Trends Biochem Sci, 24(2):68-72.
[20]Daoud H, Zhang D, McMurray F, et al., 2016. Identification of a pathogenic FTO mutation by next-generation sequencing in a newborn with growth retardation and developmental delay. J Med Genet, 53(3):200-207.
[21]Daya M, Pujianto DA, Witjaksono F, et al., 2019. Obesity risk and preference for high dietary fat intake are determined by FTO rs9939609 gene polymorphism in selected Indonesian adults. Asia Pac J Clin Nutr, 28(1):183-191.
[22]Dina C, Meyre D, Gallina S, et al., 2007. Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet, 39(6):724-726.
[23]Dominissini D, Moshitch-Moshkovitz S, Schwartz S, et al., 2012. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature, 485(7397):201-206.
[24]Dorn LE, Lasman L, Chen J, et al., 2019. The N6-methyladenosine mRNA methylase METTL3 controls cardiac homeostasis and hypertrophy. Circulation, 139(4):533-545.
[25]el Azzouzi H, Leptidis S, Dirkx E, et al., 2013. The hypoxia-inducible microRNA cluster miR-199a~214 targets myocardial PPARδ and impairs mitochondrial fatty acid oxidation. Cell Metab, 18(3):341-354.
[26]Essop MF, 2007. Cardiac metabolic adaptations in response to chronic hypoxia. J Physiol, 584(3):715-726.
[27]Fedeles BI, Singh V, Delaney JC, et al., 2015. The AlkB family of Fe(II)/α-ketoglutarate-dependent dioxygenases: repairing nucleic acid alkylation damage and beyond. J Biol Chem, 290(34):20734-20742.
[28]Feng ZH, Li QM, Meng RS, et al., 2018. METTL3 regulates alternative splicing of MyD88 upon the lipopolysaccharide-induced inflammatory response in human dental pulp cells. J Cell Mol Med, 22(5):2558-2568.
[29]Fernández-Morera JL, Calvanese V, Rodríguez-Rodero S, et al., 2010. Epigenetic regulation of the immune system in health and disease. Tissue Antigens, 76(6):431-439.
[30]Fiechter M, Haider A, Bengs S, et al., 2019. Sex differences in the association between inflammation and ischemic heart disease. Thromb Haemost, 119(9):1471-1480.
[31]Fu Y, Dominissini D, Rechavi G, et al., 2014. Gene expression regulation mediated through reversible m6A RNA methylation. Nat Rev Genet, 15(5):293-306.
[32]Fustin JM, Doi M, Yamaguchi Y, et al., 2013. RNA-methylation-dependent RNA processing controls the speed of the circadian clock. Cell, 155(4):793-806.
[33]Gan HL, Hong L, Yang FL, et al., 2019. Progress in epigenetic modification of mRNA and the function of m6A modification. Chin J Biotechnol, 35(5):775-783 (in Chinese).
[34]https://doi.org/10.13345/j.cjb.180416
[35]Ge L, Cai Y, Ying F, et al., 2019. miR-181c-5p exacerbates hypoxia/reoxygenation-induced cardiomyocyte apoptosis via targeting PTPN4. Oxid Med Cell Longev, 2019: 1957920.
[36]Gerken T, Girard CA, Tung YCL, et al., 2007. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science, 318(5855):1469-1472.
[37]Gibney ER, Nolan CM, 2010. Epigenetics and gene expression. Heredity (Edinb), 105(1):4-13.
[38]Gilbert ER, Liu DM, 2012. Epigenetics: the missing link to understanding β-cell dysfunction in the pathogenesis of type 2 diabetes. Epigenetics, 7(8):841-852.
[39]Grandl G, Wolfrum C, 2018. Hemostasis, endothelial stress, inflammation, and the metabolic syndrome. Semin Immunopathol, 40(2):215-224.
[40]Guo MJ, Liu XH, Zheng XT, et al., 2017. m6A RNA modification determines cell fate by regulating mRNA degradation. Cell Reprogram, 19(4):225-231.
[41]Gustavsson J, Mehlig K, Leander K, et al., 2014. FTO genotype, physical activity, and coronary heart disease risk in Swedish men and women. Circ Cardiovasc Genet, 7(2):171-177.
[42]Haupt A, Thamer C, Staiger H, et al., 2009. Variation in the FTO gene influences food intake but not energy expenditure. Exp Clin Endocrinol Diabetes, 117(4):194-197.
[43]He C, 2010. Grand challenge commentary: RNA epigenetics? Nat Chem Biol, 6(12):863-865.
[44]He SK, Li XH, Chan N, et al., 2013. Review: epigenetic mechanisms in ocular disease. Mol Vis, 19:665-674.
[45]Henriques JPS, Haasdijk AP, Zijlstra F, et al., 2003. Outcome of primary angioplasty for acute myocardial infarction during routine duty hours versus during off-hours. J Am Coll Cardiol, 41(12):2138-2142.
[46]Hess ME, Hess S, Meyer KD, et al., 2013. The fat mass and obesity associated gene (Fto) regulates activity of the dopaminergic midbrain circuitry. Nat Neurosci, 16(8):1042-1048.
[47]Hou N, Wen Y, Yuan X, et al., 2017. Activation of Yap1/Taz signaling in ischemic heart disease and dilated cardiomyopathy. Exp Mol Pathol, 103(3):267-275.
[48]IL6R Genetics Consortium Emerging Risk Factors Collaboration, 2012. Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies. Lancet, 379(9822):1205-1213.
[49]Iyen B, Qureshi N, Kai J, et al., 2019. Risk of cardiovascular disease outcomes in primary care subjects with familial hypercholesterolaemia: a cohort study. Atherosclerosis, 287:8-15.
[50]James K, Weitzel LRB, Engelman CD, et al., 2003. Genome scan linkage results for longitudinal systolic blood pressure phenotypes in subjects from the Framingham Heart Study. BMC Genet, 4:S83.
[51]Jia GF, Fu Y, Zhao X, et al., 2011. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol, 7(12):885-887.
[52]Jin J, Liu YF, Huang LH, et al., 2019. Advances in epigenetic regulation of vascular aging. Rev Cardiovasc Med, 20(1):19-25.
[53]https://doi.org/10.31083/j.rcm.2019.01.3189
[54]Katada S, Sassone-Corsi P, 2010. The histone methyltransferase MLL1 permits the oscillation of circadian gene expression. Nat Struct Mol Biol, 17(12):1414-1421.
[55]Kennedy EM, Bogerd HP, Kornepati AVR, et al., 2016. Posttranscriptional m6A editing of HIV-1 mRNAs enhances viral gene expression. Cell Host Microbe, 19(5):675-685.
[56]Ketelhuth DFJ, Hansson GK, 2016. Adaptive response of T and B cells in atherosclerosis. Circ Res, 118(4):668-678.
[57]Ketelhuth DFJ, Lutgens E, Bäck M, et al., 2019. Immunometabolism and atherosclerosis: perspectives and clinical significance: a position paper from the Working Group on Atherosclerosis and Vascular Biology of the European Society of Cardiology. Cardiovasc Res, 115(9):1385-1392.
[58]Khunti K, Davies M, Majeed A, et al., 2015. Hypoglycemia and risk of cardiovascular disease and all-cause mortality in insulin-treated people with type 1 and type 2 diabetes: a cohort study. Diabetes Care, 38(2):316-322.
[59]Kmietczyk V, Riechert E, Kalinski L, et al., 2019. m6A-mRNA methylation regulates cardiac gene expression and cellular growth. Life Sci Alliance, 2(2):e201800233.
[60]https://doi.org/10.26508/lsa.201800233
[61]Koliaki C, Liatis S, Kokkinos A, 2019. Obesity and cardiovascular disease: revisiting an old relationship. Metabolism, 92:98-107.
[62]Kursawe R, Dixit VD, Scherer PE, et al., 2016. A role of the inflammasome in the low storage capacity of the abdominal subcutaneous adipose tissue in obese adolescents. Diabetes, 65(3):610-618.
[63]Lee SH, Wolf PL, Escudero R, et al., 2000. Early expression of angiogenesis factors in acute myocardial ischemia and infarction. N Engl J Med, 342(9):626-633.
[64]Legein B, Janssen EM, Theelen TL, et al., 2015. Ablation of CD8α+ dendritic cell mediated cross-presentation does not impact atherosclerosis in hyperlipidemic mice. Sci Rep, 5:15414.
[65]Li Y, Ma ZQ, Jiang S, et al., 2017. A global perspective on FOXO1 in lipid metabolism and lipid-related diseases. Prog Lipid Res, 66:42-49.
[66]Libby P, Ridker PM, Hansson GK, 2011. Progress and challenges in translating the biology of atherosclerosis. Nature, 473(7347):317-325.
[67]Libby P, Lichtman AH, Hansson GK, 2013. Immune effector mechanisms implicated in atherosclerosis: from mice to humans. Immunity, 38(6):1092-1104.
[68]Lin SB, Choe J, Du P, et al., 2016. The m6A methyltransferase METTL3 promotes translation in human cancer cells. Mol Cell, 62(3):335-345.
[69]Liu JZ, Yue YN, Han DL, et al., 2014. A METTL3– METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat Chem Biol, 10(2):93-95.
[70]Liu N, Pan T, 2015. RNA epigenetics. Transl Res, 165(1):28-35.
[71]Liu X, Lin L, Li Q, et al., 2019. ERK1/2 communicates GPCR and EGFR signaling pathways to promote CTGF-mediated hypertrophic cardiomyopathy upon Ang-II stimulation. BMC Mol Cell Biol, 20:14.
[72]Lokody I, 2014. Gene regulation: RNA methylation regulates the circadian clock. Nat Rev Genet, 15(1):3.
[73]Lu L, Liu M, Sun RR, et al., 2015. Myocardial infarction: symptoms and treatments. Cell Biochem Biophys, 72(3):865-867.
[74]Martino T, Arab S, Straume M, et al., 2004. Day/night rhythms in gene expression of the normal murine heart. J Mol Med (Berl), 82(4):256-264.
[75]Martino TA, Sole MJ, 2009. Molecular time: an often overlooked dimension to cardiovascular disease. Circ Res, 105(11):1047-1061.
[76]Mathiyalagan P, Adamiak M, Mayourian J, et al., 2019. FTO-dependent N6-methyladenosine regulates cardiac function during remodeling and repair. Circulation, 139(4):518-532.
[77]Mauer J, Luo XB, Blanjoie A, et al., 2017. Reversible methylation of m6Am in the 5' cap controls mRNA stability. Nature, 541(7637):371-375.
[78]Mazzio EA, Soliman KFA, 2012. Basic concepts of epigenetics: impact of environmental signals on gene expression. Epigenetics, 7(2):119-130.
[79]McNamara P, Seo SB, Rudic RD, et al., 2001. Regulation of CLOCK and MOP4 by nuclear hormone receptors in the vasculature: a humoral mechanism to reset a peripheral clock. Cell, 105(7):877-889.
[80]Melkani GC, Panda S, 2017. Time-restricted feeding for prevention and treatment of cardiometabolic disorders. J Physiol, 595(12):3691-3700.
[81]Meyer KD, Saletore Y, Zumbo P, et al., 2012. Comprehensive analysis of mRNA methylation reveals enrichment in 3' UTRs and near stop codons. Cell, 149(7):1635-1646.
[82]Meyer KD, Patil DP, Zhou J, et al., 2015. 5' UTR m6A promotes cap-independent translation. Cell, 163(4):999-1010.
[83]Miki T, Xu ZX, Chen-Goodspeed M, et al., 2012. PML regulates PER2 nuclear localization and circadian function. EMBO J, 31(6):1427-1439.
[84]Mitrokhin V, Nikitin A, Brovkina O, et al., 2017. Association between interleukin-6/6R gene polymorphisms and coronary artery disease in Russian population: influence of interleukin-6/6R gene polymorphisms on inflammatory markers. J Inflamm Res, 10:151-160.
[85]Mukamal KJ, Muller JE, Maclure M, et al., 2000. Increased risk of congestive heart failure among infarctions with nighttime onset. Am Heart J, 140(3):438-442.
[86]Nakahata Y, Kaluzova M, Grimaldi B, et al., 2008. The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell, 134(2):329-340.
[87]Niu YM, Zhao X, Wu YS, et al., 2013. N6-methyl-adenosine (m6A) in RNA: an old modification with a novel epigenetic function. Genomics Proteomics Bioinformatics, 11(1):8-17.
[88]Olivieri F, Albertini MC, Orciani M, et al., 2015. DNA damage response (DDR) and senescence: shuttled inflamma-miRNAs on the stage of inflammaging. Oncotarget, 6(34):35509-35521.
[89]https://doi.org/10.18632/oncotarget.5899
[90]Ortiz-Barahona A, Villar D, Pescador N, et al., 2010. Genome-wide identification of hypoxia-inducible factor binding sites and target genes by a probabilistic model integrating transcription-profiling data and in silico binding site prediction. Nucleic Acids Res, 38(7):2332-2345.
[91]Panneerdoss S, Eedunuri VK, Yadav P, et al., 2018. Cross-talk among writers, readers, and erasers of m6A regulates cancer growth and progression. Sci Adv, 4(10):eaar8263.
[92]Parashar NC, Parashar G, Nayyar H, et al., 2018. N6-adenine DNA methylation demystified in eukaryotic genome: from biology to pathology. Biochimie, 144:56-62.
[93]Pastore N, Brady OA, Diab HI, et al., 2016. TFEB and TFE3 cooperate in the regulation of the innate immune response in activated macrophages. Autophagy, 12(8):1240-1258.
[94]Patil DP, Pickering BF, Jaffrey SR, 2018. Reading m6A in the transcriptome: m6A-binding proteins. Trends Cell Biol, 28(2):113-127.
[95]Peña MSB, Rollins A, 2017. Environmental exposures and cardiovascular disease: a challenge for health and development in low-and middle-income countries. Cardiol Clin, 35(1):71-86.
[96]Reese DE, Mikawa T, Bader DM, 2002. Development of the coronary vessel system. Circ Res, 91(9):761-768.
[97]Rodriguez H, Drouin R, Holmquist GP, et al., 1997. A hot spot for hydrogen peroxide-induced damage in the human hypoxia-inducible factor 1 binding site of the PGK 1 gene. Arch Biochem Biophys, 338(2):207-212.
[98]Rodriguez-Rodero S, Fernández-Morera JL, Fernandez AF, et al., 2010. Epigenetic regulation of aging. Discov Med, 10(52):225-233.
[99]Roignant JY, Soller M, 2017. m6A in mRNA: an ancient mechanism for fine-tuning gene expression. Trends Genet, 33(6):380-390.
[100]Scuteri A, Sanna S, Chen WM, et al., 2007. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet, 3(7):e115.
[101]Shen F, Huang W, Huang JT, et al., 2015. Decreased N6-methyladenosine in peripheral blood RNA from diabetic patients is associated with FTO expression rather than ALKBH5. J Clin Endocrinol Metab, 100(1):E148-E154.
[102]Singhal A, Arora G, Sajid A, et al., 2013. Regulation of homocysteine metabolism by Mycobacterium tuberculosis S-adenosylhomocysteine hydrolase. Sci Rep, 3:2264.
[103]Smart N, Risebro CA, Melville AAD, et al., 2007. Thymosin β-4 is essential for coronary vessel development and promotes neovascularization via adult epicardium. Ann N Y Acad Sci, 1112(1):171-188.
[104]Smith AJP, Humphries SE, 2009. Cytokine and cytokine receptor gene polymorphisms and their functionality. Cytokine Growth Factor Rev, 20(1):43-59.
[105]Smith TG, Robbins PA, Ratcliffe PJ, 2008. The human side of hypoxia-inducible factor. Br J Haematol, 141(3):325-334.
[106]Smith ZD, Chan MM, Mikkelsen TS, et al., 2012. A unique regulatory phase of DNA methylation in the early mammalian embryo. Nature, 484(7394):339-344.
[107]Song HW, Feng X, Zhang H, et al., 2019. METTL3 and ALKBH5 oppositely regulate m6A modification of TFEB mRNA, which dictates the fate of hypoxia/reoxygenation-treated cardiomyocytes. Autophagy, 15(8):1419-1437.
[108]Souness JE, Stouffer JE, de Sanchez VC, 1982. Effect of N6- methyladenosine on fat-cell glucose metabolism: evidence for two modes of action. Biochem Pharmacol, 31(24):3961-3971.
[109]Speakman JR, Rance KA, Johnstone AM, 2008. Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure. Obesity (Silver Spring), 16(8):1961-1965.
[110]Tan FL, Moravec CS, Li JB, et al., 2002. The gene expression fingerprint of human heart failure. Proc Natl Acad Sci USA, 99(17):11387-11392.
[111]Timpson NJ, Emmett PM, Frayling TM, et al., 2008. The fat mass- and obesity-associated locus and dietary intake in children. Am J Clin Nutr, 88(4):971-978.
[112]van Wijk B, van den Berg G, Abu-Issa R, et al., 2009. Epicardium and myocardium separate from a common precursor pool by crosstalk between bone morphogenetic protein-and fibroblast growth factor-signaling pathways. Circ Res, 105(5):431-441.
[113]Wang CY, Shie SS, Wen MS, et al., 2015. Loss of FTO in adipose tissue decreases Angptl4 translation and alters triglyceride metabolism. Sci Signal, 8(407):ra127.
[114]Wang X, He C, 2014. Reading RNA methylation codes through methyl-specific binding proteins. RNA Biol, 11(6):669-672.
[115]Wang Y, Li Y, Toth JI, et al., 2014. N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nat Cell Biol, 16(2):191-198.
[116]Weber C, Noels H, 2011. Atherosclerosis: current pathogenesis and therapeutic options. Nat Med, 17(11):1410-1422.
[117]Wei CM, Moss B, 1977. Nucleotide sequences at the N6-methyladenosine sites of HeLa cell messenger ribonucleic acid. Biochemistry, 16(8):1672-1676.
[118]Wei WQ, Ji XY, Guo XQ, et al., 2017. Regulatory role of N6-methyladenosine (m6A) methylation in RNA processing and human diseases. J Cell Biochem, 118(9):2534-2543.
[119]Wilkins AK, Barton PI, Tidor B, 2007. The Per2 negative feedback loop sets the period in the mammalian circadian clock mechanism. PLoS Comput Biol, 3(12):e242.
[120]Winter EM, Groot ACGD, 2007. Epicardium-derived cells in cardiogenesis and cardiac regeneration. Cell Mol Life Sci, 64(6):692-703.
[121]Wong C, Kanetsky P, Raj D, 2008. Genetic polymorphisms of the RAS-cytokine pathway and chronic kidney disease. Pediatr Nephrol, 23(7):1037-1051.
[122]Xuan Y, Wang LN, Zhi H, et al., 2016. Association between 3 IL-10 gene polymorphisms and cardiovascular disease risk: systematic review with meta-analysis and trial sequential analysis. Medicine (Baltimore), 95(6):e2846.
[123]Yang Y, Shen F, Huang W, et al., 2019. Glucose is involved in the dynamic regulation of m6A in patients with type 2 diabetes. J Clin Endocrinol Metab, 104(3):665-673.
[124]Zhong SL, Li HY, Bodi Z, et al., 2008. MTA is an Arabidopsis messenger RNA adenosine methylase and interacts with a homolog of a sex-specific splicing factor. Plant Cell, 20(5):1278-1288.
[125]Zhou B, Ma Q, Rajagopal S, et al., 2008. Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature, 454(7200):109-113.
Open peer comments: Debate/Discuss/Question/Opinion
<1>