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Review Articles

Epigenetics in drug disposition & drug therapy: symposium report of the 24th North American meeting of the International Society for the Study of Xenobiotics (ISSX)

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Pages 318-330 | Received 30 Jun 2022, Accepted 10 Jul 2022, Published online: 24 Aug 2022

References

  • Agundez JA. 2004. Cytochrome P450 gene polymorphism and cancer. Curr Drug Metab. 5(3):211–224.
  • Ahmed S, Zhou Z, Zhou J, Chen SQ. 2016. Pharmacogenomics of drug metabolizing enzymes and transporters: relevance to precision medicine. Genom Proteom Bioinf. 14(5):298–313.
  • Baek D, Villen J, Shin C, Camargo FD, Gygi SP, Bartel DP. 2008. The impact of microRNAs on protein output. Nature. 455(7209):64–71.
  • Balkrishna D, Sumant O. 2022. Epigenetics market by products (kits, reagents, enzymes, instruments), by application (oncology, non oncology), by end user (academic and research institutes, pharmaceutical and biotechnology companies, contract research organizations): global opportunity analysis and industry forecast, 2020-2030. Portland, OR: Allied Market Research; [accessed 2022 April 28]. https://www.alliedmarketresearch.com/epigenetics-market.
  • Balliet RM, Chen G, Gallagher CJ, Dellinger RW, Sun D, Lazarus P. 2009. Characterization of UGTs active against SAHA and association between SAHA glucuronidation activity phenotype with UGT genotype. Cancer Res. 69(7):2981–2989.
  • Bayoumi A, Grønbæk H, George J, Eslam M. 2020. The epigenetic drug discovery landscape for metabolic-associated fatty liver disease. Trends Genet. 36(6):429–441.
  • Belanger A, Hum DW, Beaulieu M, Levesque E, Guillemette C, Tchernof A, Belanger G, Turgeon D, Dubois S. 1998. Characterization and regulation of UDP-glucuronosyltransferases in steroid target tissues. J Steroid Biochem Mol Biol. 65(1–6):301–310.
  • Benayoun BA, Pollina EA, Brunet A. 2015. Epigenetic regulation of ageing: linking environmental inputs to genomic stability. Nat Rev Mol Cell Biol. 16(10):593–610.
  • Bolha L, Ravnik-Glavač M, Glavač D. 2017. Long noncoding RNAs as biomarkers in cancer. Dis Markers. 2017:7243968.
  • Bonder MJ, Kasela S, Kals M, Tamm R, Lokk K, Barragan I, Buurman WA, Deelen P, Greve JW, Ivanov M, et al. 2014. Genetic and epigenetic regulation of gene expression in fetal and adult human livers. BMC Genomics. 15(1):860.
  • Bosma PJ, Seppen J, Goldhoorn B, Bakker C, Oude Elferink RP, Chowdhury JR, Chowdhury NR, Jansen PL. 1994. Bilirubin UDP-glucuronosyltransferase 1 is the only relevant bilirubin glucuronidating isoform in man. J Biol Chem. 269(27):17960–17964.
  • Budnitz DS, Lovegrove MC, Shehab N, Richards CL. 2011. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med. 365(21):2002–2012.
  • Carthew RW, Sontheimer EJ. 2009. Origins and mechanisms of miRNAs and siRNAs. Cell. 136(4):642–655.
  • Cascorbi I, Schwab M. 2016. Epigenetics in drug response. Clin Pharmacol Ther. 99(5):468–470.
  • Chen L, Bao Y, Piekos SC, Zhu K, Zhang L, Zhong XB. 2018. A transcriptional regulatory network containing nuclear receptors and long noncoding RNAs controls basal and drug-induced expression of cytochrome P450s in HepaRG cells. Mol Pharmacol. 94(1):749–759.
  • Chen L, Wang P, Manautou JE, Zhong XB. 2020. Knockdown of long noncoding RNAs hepatocyte nuclear factor 1α antisense RNA 1 and hepatocyte nuclear factor 4α antisense RNA 1 alters susceptibility of acetaminophen-induced cytotoxicity in HepaRG cells. Mol Pharmacol. 97(4):278–286.
  • Chen Y, Zeng L, Wang Y, Tolleson WH, Knox B, Chen S, Ren Z, Guo L, Mei N, Qian F, et al. 2017. The expression, induction and pharmacological activity of CYP1A2 are post-transcriptionally regulated by microRNA hsa-miR-132-5p. Biochem Pharmacol. 145:178–191.
  • Cheng G. 2015. Circulating miRNAs: roles in cancer diagnosis, prognosis and therapy. Adv Drug Deliv Rev. 81:75–93.
  • Condrat CE, Thompson DC, Barbu MG, Bugnar OL, Boboc A, Cretoiu D, Suciu N, Cretoiu SM, Voinea SC. 2020. miRNAs as biomarkers in disease: Latest findings regarding their role in diagnosis and prognosis. cells. 9(2):276.
  • Court MH, Duan SX, von Moltke LL, Greenblatt DJ, Patten CJ, Miners JO, Mackenzie PI. 2001. Interindividual variability in acetaminophen glucuronidation by human liver microsomes: identification of relevant acetaminophen UDP-glucuronosyltransferase isoforms. J Pharmacol Exp Ther. 299(3):998–1006.
  • Court MH, Von Moltke LL, Shader RI, Greenblatt DJ. 1997. Biotransformation of chlorzoxazone by hepatic microsomes from humans and ten other mammalian species. Biopharm Drug Dispos. 18(3):213–226.
  • Dannenberg LO, Edenberg HJ. 2006. Epigenetics of gene expression in human hepatoma cells: expression profiling the response to inhibition of DNA methylation and histone deacetylation. BMC Genomics. 7(1):181.
  • Dluzen DF, Lazarus P. 2015. MicroRNA regulation of the major drug-metabolizing enzymes and related transcription factors. Drug Metab Rev. 47(3):320–334.
  • Dluzen DF, Sutliff AK, Chen G, Watson CJ, Ishmael FT, Lazarus P. 2016. Regulation of UGT2B expression and activity by miR-216b-5p in liver cancer cell lines. J Pharmacol Exp Ther. 359(1):182–193.
  • Einolf HJ, Chen L, Fahmi OA, Gibson CR, Obach RS, Shebley M, Silva J, Sinz MW, Unadkat JD, Zhang L, et al. 2014. Evaluation of various static and dynamic modeling methods to predict clinical CYP3A induction using in vitro CYP3A4 mRNA induction data. Clin Pharmacol Ther. 95(2):179–188.
  • Feil R, Fraga MF. 2012. Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet. 13(2):97–109.
  • Feinberg AP. 2007. Phenotypic plasticity and the epigenetics of human disease. Nature. 447(7143):433–440.
  • Fisel P, Schaeffeler E, Schwab M. 2016. DNA methylation of ADME genes. Clin Pharmacol Ther. 99(5):512–527.
  • Fowler S, Morcos PN, Cleary Y, Martin-Facklam M, Parrott N, Gertz M, Yu L. 2017. Progress in prediction and interpretation of clinically relevant metabolic drug-drug interactions: a minireview illustrating recent developments and current opportunities. Curr Pharmacol Rep. 3(1):36–49.
  • Fraga MF, Esteller M. 2007. Epigenetics and aging: the targets and the marks. Trends Genet. 23(8):413–418.
  • Guo H, Ingolia NT, Weissman JS, Bartel DP. 2010. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 466(7308):835–840.
  • Habano W, Kawamura K, Iizuka N, Terashima J, Sugai T, Ozawa S. 2015. Analysis of DNA methylation landscape reveals the roles of DNA methylation in the regulation of drug metabolizing enzymes. Clin Epigenetics. 7:105.
  • Handel AE, Ebers GC, Ramagopalan SV. 2010. Epigenetics: molecular mechanisms and implications for disease. Trends Mol Med. 16(1):7–16.
  • Hannon E, Lunnon K, Schalkwyk L, Mill J. 2015. Interindividual methylomic variation across blood, cortex, and cerebellum: implications for epigenetic studies of neurological and neuropsychiatric phenotypes. Epigenetics. 10(11):1024–1032.
  • Heerboth S, Lapinska K, Snyder N, Leary M, Rollinson S, Sarkar S. 2014. Use of epigenetic drugs in disease: an overview. Genet Epigenet. 6:9–19.
  • Honkakoski P, Negishi M. 2000. Regulation of cytochrome P450 (CYP) genes by nuclear receptors. Biochem J. 347(Pt 2):321–337.
  • Horvath S. 2013. DNA methylation age of human tissues and cell types. Genome Biol. 14(10):R115.
  • Huntzinger E, Izaurralde E. 2011. Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nat Rev Genet. 12(2):99–110.
  • Ingelman-Sundberg M, Zhong XB, Hankinson O, Beedanagari S, Yu AM, Peng L, Osawa Y. 2013. Potential role of epigenetic mechanisms in the regulation of drug metabolism and transport. Drug Metab Dispos. 41(10):1725–1731.
  • Jin Y, Yu D, Tolleson WH, Knox B, Wang Y, Chen S, Ren Z, Deng H, Guo Y, Ning B. 2016. MicroRNA hsa-miR-25-3p suppresses the expression and drug induction of CYP2B6 in human hepatocytes. Biochem Pharmacol. 113:88–96.
  • Komagata S, Nakajima M, Takagi S, Mohri T, Taniya T, Yokoi T. 2009. Human CYP24 catalyzing the inactivation of calcitriol is post-transcriptionally regulated by miR-125b. Mol Pharmacol. 76(4):702–709.
  • Kringel D, Malkusch S, Lötsch J. 2021. Drugs and epigenetic molecular functions. a pharmacological data scientometric analysis. IJMS. 22(14):7250.
  • Kronfol MM, Abudahab S, Dozmorov MG, Jahr FM, Halquist MS, McRae M, Wijesinghe DS, Price ET, Slattum PW, McClay JL. 2021. Histone acetylation at the sulfotransferase 1a1 gene is associated with its hepatic expression in normal aging. Pharmacogenet Genomics. 31(9):207–214.
  • Kronfol MM, Dozmorov MG, Huang R, Slattum PW, McClay JL. 2017. The role of epigenomics in personalized medicine. Expert Rev Precis Med Drug Dev. 2(1):33–45.
  • Kronfol MM, Jahr FM, Dozmorov MG, Phansalkar PS, Xie LY, Aberg KA, McRae M, Price ET, Slattum PW, Gerk PM, et al. 2020. DNA methylation and histone acetylation changes to cytochrome P450 2E1 regulation in normal aging and impact on rates of drug metabolism in the liver. Geroscience. 42(3):819–832.
  • Lauschke VM, Zhou Y, Ingelman-Sundberg M. 2019. Novel genetic and epigenetic factors of importance for inter-individual differences in drug disposition, response and toxicity. Pharmacol Ther. 197:122–152.
  • Li E. 2002. Chromatin modification and epigenetic reprogramming in mammalian development. Nat Rev Genet. 3(9):662–673.
  • Li D, Knox B, Chen S, Wu L, Tolleson WH, Liu Z, Yu D, Guo L, Tong W, Ning B. 2019a. MicroRNAs hsa-miR-495-3p and hsa-miR-486-5p suppress basal and rifampicin-induced expression of human sulfotransferase 2A1 (SULT2A1) by facilitating mRNA degradation. Biochem Pharmacol. 169:113617.
  • Li D, Knox B, Gong B, Chen S, Guo L, Liu Z, Tong W, Ning B. 2021. Identification of translational microRNA biomarker candidates for ketoconazole-induced liver injury using next-generation sequencing. Toxicol Sci. 179(1):31–43.
  • Li Y, Li Y, Zheng G, Zhu L, Wang J, Mu S, Ren Q, Feng F. 2018. Cytochrome P450 1A1 and 1B1 promoter CpG island methylation regulates rat liver injury induced by isoniazid. Mol Med Rep. 17(1):753–762.
  • Li D, Tolleson WH, Yu D, Chen S, Guo L, Xiao W, Tong W, Ning B. 2019b. Regulation of cytochrome P450 expression by microRNAs and long noncoding RNAs: Epigenetic mechanisms in environmental toxicology and carcinogenesis. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 37(3):180–214.
  • Li D, Wu L, Knox B, Chen S, Tolleson WH, Liu F, Yu D, Guo L, Tong W, Ning B. 2020. Long noncoding RNA LINC00844-mediated molecular network regulates expression of drug metabolizing enzymes and nuclear receptors in human liver cells. Arch Toxicol. 94(5):1637–1653.
  • Lowe R, Slodkowicz G, Goldman N, Rakyan VK. 2015. The human blood DNA methylome displays a highly distinctive profile compared with other somatic tissues. Epigenetics. 10(4):274–281.
  • Lu C, Di L. 2020. In vitro and in vivo methods to assess pharmacokinetic drug- drug interactions in drug discovery and development. Biopharm Drug Dispos. 41(1–2):3–31.
  • McClay JL, Aberg KA, Clark SL, Nerella S, Kumar G, Xie LY, Hudson AD, Harada A, Hultman CM, Magnusson PK, et al. 2014. A methylome-wide study of aging using massively parallel sequencing of the methyl-CpG-enriched genomic fraction from blood in over 700 subjects. Hum Mol Genet. 23(5):1175–1185.
  • Miao L, Yao H, Li C, Pu M, Yao X, Yang H, Qi X, Ren J, Wang Y. 2016. A dual inhibition: microRNA-552 suppresses both transcription and translation of cytochrome P450 2E1. Biochim Biophys Acta. 1859(4):650–662.
  • Lorico A, Corbeil D, Pawelek JM, Alessandro R. 2015. Transmission of information in neoplasia by extracellular vesicles. Hindawi. 2015:1–2.
  • Mohri T, Nakajima M, Fukami T, Takamiya M, Aoki Y, Yokoi T. 2010. Human CYP2E1 is regulated by miR-378. Biochem Pharmacol. 79(7):1045–1052.
  • Mukherji S, Ebert MS, Zheng GX, Tsang JS, Sharp PA, van Oudenaarden A. 2011. MicroRNAs can generate thresholds in target gene expression. Nat Genet. 43(9):854–859.
  • Nagar S, Remmel RP. 2006. Uridine diphosphoglucuronosyltransferase pharmacogenetics and cancer. Oncogene. 25(11):1659–1672.
  • Nakano M, Mohri T, Fukami T, Takamiya M, Aoki Y, McLeod HL, Nakajima M. 2015. Single-nucleotide polymorphisms in cytochrome P450 2E1 (CYP2E1) 3’-untranslated region affect the regulation of CYP2E1 by miR-570. Drug Metab Dispos. 43(10):1450–1457.
  • Nguyen KV. 2019. Potential epigenomic co-management in rare diseases and epigenetic therapy. Nucleosides Nucleotides Nucleic Acids. 38(10):752–780.
  • Ning B, Yu D, Yu AM. 2019. Advances and challenges in studying noncoding RNA regulation of drug metabolism and development of RNA therapeutics. Biochem Pharmacol. 169:113638.
  • Pan YZ, Gao W, Yu AM. 2009. MicroRNAs regulate CYP3A4 expression via direct and indirect targeting. Drug Metab Dispos. 37(10):2112–2117.
  • Pan X, Kent R, Won KJ, Jeong H. 2017. Cholic acid feeding leads to increased CYP2D6 expression in CYP2D6-humanized mice. Drug Metab Dispos. 45(4):346–352.
  • Peters MJ, Joehanes R, Pilling LC, Schurmann C, Conneely KN, Powell J, Reinmaa E, Sutphin GL, Zhernakova A, Schramm K, et al. 2015. The transcriptional landscape of age in human peripheral blood. Nat Commun. 6:8570.
  • Prachayasittikul V, Prathipati P, Pratiwi R, Phanus-Umporn C, Malik AA, Schaduangrat N, Seenprachawong K, Wongchitrat P, Supokawej A, Prachayasittikul V, et al. 2017. Exploring the epigenetic drug discovery landscape. Expert Opin Drug Discov. 12(4):345–362.
  • Rasool M, Malik A, Naseer MI, Manan A, Ansari S, Begum I, Qazi MH, Pushparaj P, Abuzenadah AM, Al-Qahtani MH, et al. 2015. The role of epigenetics in personalized medicine: challenges and opportunities. BMC Med Genomics. 8(Suppl 1):S5.
  • Reynolds LM, Taylor JR, Ding J, Lohman K, Johnson C, Siscovick D, Burke G, Post W, Shea S, Jacobs DR Jr, et al. 2014. Age-related variations in the methylome associated with gene expression in human monocytes and T cells. Nat Commun. 5:5366.
  • Routledge PA, O’Mahony MS, Woodhouse KW. 2004. Adverse drug reactions in elderly patients. Br J Clin Pharmacol. 57(2):121–126.
  • Russell LE, Zhou Y, Almousa AA, Sodhi JK, Nwabufo CK, Lauschke VM. 2021. Pharmacogenomics in the era of next generation sequencing– from byte to bedside. Drug Metab Rev. 53(2):253–278.
  • Savolainen VT, Pajarinen J, Perola M, Penttilä A, Karhunen PJ. 1997. Polymorphism in the cytochrome P450 2E1 gene and the risk of alcoholic liver disease. J Hepatol. 26(1):55–61.
  • Selbach M, Schwanhausser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N. 2008. Widespread changes in protein synthesis induced by microRNAs. Nature. 455(7209):58–63.
  • Sim SC, Kacevska M, Ingelman-Sundberg M. 2013. Pharmacogenomics of drug-metabolizing enzymes: a recent update on clinical implications and endogenous effects. Pharmacogenomics J. 13(1):1–11.
  • Steegenga WT, Boekschoten MV, Lute C, Hooiveld GJ, de Groot PJ, Morris TJ, Teschendorff AE, Butcher LM, Beck S, Müller M. 2014. Genome-wide age-related changes in DNA methylation and gene expression in human PBMCs. Age (Dordr). 36(3):9648.
  • Stern AM, Schurdak ME, Bahar I, Berg JM, Taylor DL. 2016. A perspective on implementing a quantitative systems pharmacology platform for drug discovery and the advancement of personalized medicine. J Biomol Screen. 21(6):521–534.
  • Stricker SH, Köferle A, Beck S. 2017. From profiles to function in epigenomics. Nat Rev Genet. 18(1):51–66.
  • Sun D, Jones NR, Manni A, Lazarus P. 2013. Characterization of raloxifene glucuronidation: potential role of UGT1A8 genotype on raloxifene metabolism in vivo. Cancer Prev Res. 6(7):719–730.
  • Sutliff AK, Shi J, Watson CJW, Hunt MS, Chen G, Zhu HJ, Lazarus P. 2019. Potential regulation of UGT2B10 and UGT2B7 by miR-485-5p in human liver. Mol Pharmacol. 96(6):674–682.
  • Takagi S, Nakajima M, Mohri T, Yokoi T. 2008. Post-transcriptional regulation of human pregnane X receptor by micro-RNA affects the expression of cytochrome P450 3A4. J Biol Chem. 283(15):9674–9680.
  • Tang X, Chen S. 2015. Epigenetic regulation of cytochrome P450 enzymes and clinical implication. Curr Drug Metab. 16(2):86–96.
  • Treyer A, Ullah M, Parrott N, Molitor B, Fowler S, Artursson P. 2019. Impact of intracellular concentrations on metabolic drug-drug interaction studies. Aaps J. 21(5):1–10.
  • Tseng E, Eng H, Lin J, Cerny MA, Tess DA, Goosen TC, Obach RS. 2021. Static and dynamic projections of drug-drug interactions caused by cytochrome P450 3A time-dependent inhibitors measured in human liver microsomes and hepatocytes. Drug Metab Dispos. 49(10):947–960.
  • Tsuchiya Y, Nakajima M, Takagi S, Taniya T, Yokoi T. 2006. MicroRNA regulates the expression of human cytochrome P450 1B1. Cancer Res. 66(18):9090–9098.
  • Wang J, Yu L, Jiang H, Zheng X, Zeng S. 2020. Epigenetic regulation of differentially expressed drug-metabolizing enzymes in cancer. Drug Metab Dispos. 48(9):759–768.
  • Wang Y, Yu D, Tolleson WH, Yu LR, Green B, Zeng L, Chen Y, Chen S, Ren Z, Guo L, et al. 2017. A systematic evaluation of microRNAs in regulating human hepatic CYP2E1. Biochem Pharmacol. 138:174–184.
  • Winkle M, El-Daly SM, Fabbri M, Calin GA. 2021. Noncoding RNA therapeutics – challenges and potential solutions. Nat Rev Drug Discov. 20(8):629–651.
  • Yadav J, Korzekwa K, Nagar S. 2018. Improved predictions of drug–drug interactions mediated by time-dependent inhibition of CYP3A. Mol Pharm. 15(5):1979–1995.
  • Yadav J, Paragas E, Korzekwa K, Nagar S. 2020. Time-dependent enzyme inactivation: numerical analyses of in vitro data and prediction of drug-drug interactions. Pharmacol Ther. 206:107449.
  • Yu D, Chen S, Li D, Knox B, Guo L, Ning B. 2020. FREMSA: a method that provides direct evidence of the interaction between microRNA and mRNA. Methods Mol Biol. 2102:557–566.
  • Yu D, Green B, Marrone A, Guo Y, Kadlubar S, Lin D, Fuscoe J, Pogribny I, Ning B. 2015. Suppression of CYP2C9 by microRNA hsa-miR-128-3p in human liver cells and association with hepatocellular carcinoma. Sci Rep. 5:8534.
  • Yu D, Wu L, Gill P, Tolleson WH, Chen S, Sun J, Knox B, Jin Y, Xiao W, Hong H, et al. 2018. Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 92(2):845–858.
  • Zanger UM, Schwab M. 2013. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther. 138(1):103–141.
  • Zeng L, Chen Y, Wang Y, Yu LR, Knox B, Chen J, Shi T, Chen S, Ren Z, Guo L, et al. 2017. MicroRNA hsa-miR-370-3p suppresses the expression and induction of CYP2D6 by facilitating mRNA degradation. Biochem Pharmacol. 140:139–149.
  • Zeng L, Li D, Tong W, Shi T, Ning B. 2021. Biochemical features and mutations of key proteins in SARS-CoV-2 and their impacts on RNA therapeutics. Biochem Pharmacol. 189:114424.
  • Zhou SF, Liu JP, Chowbay B. 2009. Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug Metab Rev. 41(2):89–295.

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