{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T16:17:45Z","timestamp":1789834665908,"version":"4.0.1"},"reference-count":69,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2017,10,5]],"date-time":"2017-10-05T00:00:00Z","timestamp":1507161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Epigenetic mechanisms play an important role in the regulation of the Growth Hormone- Insulin-like Growth Factor 1 (GH-IGF1) axis and in processes for controlling long bone growth, and carbohydrate and lipid metabolism. Improvement of methodologies that allow for the assessment of epigenetic regulation have contributed enormously to the understanding of GH action, but many questions still remain to be clarified. The reversible nature of epigenetic factors and, particularly, their role as mediators between the genome and the environment, make them viable therapeutic target candidates. Rather than reviewing the molecular and epigenetic pathways regulated by GH action, in this review we have focused on the use of epigenetic modulators as potential drugs to improve the GH response. We first discuss recent progress in the understanding of intracellular molecular mechanisms controlling GH and IGF-I action. We then emphasize current advances in genetic and epigenetic mechanisms that control gene expression, and which support a key role for epigenetic regulation in the cascade of intracellular events that trigger GH action when coupled to its receptor. Thirdly, we focus on fetal programming and epigenetic regulation at the IGF1 locus. We then discuss epigenetic alterations in intrauterine growth retardation, and the possibility for a potential epigenetic pharmaceutical approach in short stature associated with this fetal condition. Lastly, we review an example of epigenetic therapeutics in the context of growth-related epigenetic deregulation disorders. The advance of our understanding of epigenetic changes and the impact they are having on new forms of therapy creates exciting prospects for the future.<\/jats:p>","DOI":"10.3390\/ijms18101624","type":"journal-article","created":{"date-parts":[[2017,10,5]],"date-time":"2017-10-05T12:38:32Z","timestamp":1507207112000},"page":"1624","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["GH\/IGF-1 Signaling and Current Knowledge of Epigenetics; a Review and Considerations on Possible Therapeutic Options"],"prefix":"10.3390","volume":"18","author":[{"given":"Francisco","family":"\u00c1lvarez-Nava","sequence":"first","affiliation":[{"name":"Biological Sciences School, Faculty of Biological Sciences, Central University of Ecuador, Quito 999165, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Lanes","sequence":"additional","affiliation":[{"name":"Pediatric Endocrine Unit, Hospital de Cl\u00ednicas Caracas, Caracas 999188, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,10,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.ghir.2005.07.001","article-title":"Influence of the crosstalk between growth hormone and insulin signalling on the modulation of insulin sensitivity","volume":"15","author":"Dominici","year":"2005","journal-title":"Growth Horm. IGF Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1126\/science.256.5064.1677","article-title":"Rational Design of Potent Antagonists to the Human Growth Hormone Receptor","volume":"256","author":"Fuh","year":"1992","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1677\/jme.1.01933","article-title":"New insights into growth hormone action","volume":"36","author":"Waters","year":"2006","journal-title":"J. Mol. Endocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/nsmb977","article-title":"Model for growth hormone receptor activation based on subunit rotation within a receptor dimer","volume":"12","author":"Brown","year":"2005","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"17000","DOI":"10.1074\/jbc.275.22.17000","article-title":"Growth hormone (GH)-independent dimerization of GH receptor by a leucine zipper results in constitutive activation","volume":"275","author":"Behncken","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1101\/gr.5217506","article-title":"Tissue-specific expression and regulation of sexually dimorphic genes in mice\\r10.1101\/gr.5217506","volume":"16","author":"Yang","year":"2006","journal-title":"Genome Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1677\/jme.0.0180213","article-title":"The role of GH receptor tyrosine phosphorylation in Stat5 activation","volume":"18","author":"Hansen","year":"1997","journal-title":"J. Mol. Endocrinol."},{"key":"ref_8","first-page":"519","article-title":"The Role of the Growth Hormone ( GH ) Receptor and JAKI and JAK2 Kinases in the Activation of Stats 1, 3, and 5 by GH","volume":"10","author":"Smit","year":"1996","journal-title":"Mol. Endocrinol."},{"key":"ref_9","first-page":"1906","article-title":"Inhibition of growth hormone action in models of inflammation","volume":"55455","author":"Bergad","year":"2010","journal-title":"Am. J. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1210\/me.2006-0096","article-title":"In Vivo Transcript Profiling and Phylogenetic Analysis Identifies Suppressor of Cytokine Signaling 2 as a Direct Signal Transducer and Activator of Transcription 5b Target in Liver","volume":"21","author":"Vidal","year":"2007","journal-title":"Mol. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5929","DOI":"10.1074\/jbc.271.10.5929","article-title":"Growth hormone activation of Stat 1, Stat 3, and Stat 5 in rat liver: Differential kinetics of hormone desensitization and growth hormone stimulation of both tyrosine phosphorylation and serine\/threonine phosphorylation","volume":"271","author":"Ram","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_12","first-page":"508","article-title":"Characterization and Cloning of STAT5 from IM-9 Cells and Its Activation by Growth Hormone","volume":"10","author":"Silva","year":"1996","journal-title":"Mol. Endocrinol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.1073\/pnas.92.7.3041","article-title":"Spacing of palindromic half sites as a determinant of selective STAT (signal transducers and activators of transcription) DNA binding and transcriptional activity","volume":"92","author":"Seidel","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1210\/mend.11.4.9904","article-title":"Regulation of signal transducer and activator of transcription (STAT) 5b activation by the temporal pattern of growth hormone stimulation","volume":"11","author":"Gebert","year":"1997","journal-title":"Mol. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1210\/endo.137.1.8536642","article-title":"Acute nuclear actions of growth hormone (GH): Cycloheximide inhibits inducible activator protein-1 activity, but does not block GH-regulated signal transducer and activator of transcription activation or gene expression","volume":"137","author":"Gronowski","year":"1996","journal-title":"Endocrinology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1006\/dbio.2000.9975","article-title":"Roles of Growth Hormone and Insulin-like Growth Factor 1 in Mouse Postnatal Growth","volume":"229","author":"Lupu","year":"2001","journal-title":"Dev. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1530\/JOE-16-0606","article-title":"Attenuation of epidermal growth factor (EGF) signaling by growth hormone (GH)","volume":"233","author":"Gonzalez","year":"2017","journal-title":"J. Endocrinol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.imbio.2008.11.013","article-title":"Growth hormone-induced production of cytokines in murine peritoneal macrophages in vitro: Role of JAK\/STAT, PI3K, PKC and MAP kinases","volume":"214","author":"Tripathi","year":"2009","journal-title":"Immunobiology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1210\/me.2010-0234","article-title":"Defining the epigenetic actions of growth hormone: Acute chromatin changes accompany GH-activated gene transcription","volume":"24","author":"Chia","year":"2010","journal-title":"Mol. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.tem.2012.01.001","article-title":"Mapping the growth hormone-Stat5b-IGF-I transcriptional circuit","volume":"23","author":"Rotwein","year":"2012","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fendo.2013.00039","article-title":"The regulation of IGF-1 gene transcription and splicing during development and aging","volume":"4","author":"Oberbauer","year":"2013","journal-title":"Front. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7873","DOI":"10.1093\/nar\/14.20.7873","article-title":"Sequences of liver cDNAs encoding two different mouse insulin like growth factor I precursors","volume":"14","author":"Bell","year":"1986","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1210\/mend-2-6-528","article-title":"Distribution and regulation of rat insulin-like growth factor I messenger ribonucleic acids encoding alternative carboxyterminal E-peptides: Evidence for differential processing and regulation in liver","volume":"2","author":"Lowe","year":"1988","journal-title":"Mol. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1210\/endo-127-3-1550","article-title":"Different half-lives of insulin-like growth factor I mRNAs that differ in length of 3' untranslated sequence","volume":"127","author":"Hepler","year":"1990","journal-title":"Endocrinology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1139\/h06-054","article-title":"The ABCs of IGF-I isoforms: Impact on muscle hypertrophy and implications for repair","volume":"31","author":"Barton","year":"2006","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1210\/en.2009-1217","article-title":"Minireview: Mechano-growth factor: A putative product of IGF-I gene expression involved in tissue repair and regeneration","volume":"151","author":"Matheny","year":"2010","journal-title":"Endocrinology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"17636","DOI":"10.1074\/jbc.M110.117697","article-title":"Dispersed chromosomal Stat5b-binding elements mediate growth hormone-activated insulin-like growth factor-I gene transcription","volume":"285","author":"Chia","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_28","first-page":"51261","article-title":"Mechanisms of Growth Hormone (GH) Action prior to the onset of transcription from both major and","volume":"278","author":"Woelfle","year":"2003","journal-title":"Biochemistry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10955","DOI":"10.1074\/jbc.M412808200","article-title":"Identification of a Distal STAT5-binding DNA region that may mediate growth hormone regulation of insulin-like growth factor-I gene expression *","volume":"280","author":"Wang","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1210\/en.2007-1344","article-title":"Growth hormone regulation of insulin-like growth factor-I gene expression may be mediated by multiple distal signal transducer and activator of transcription 5 binding sites","volume":"149","author":"Eleswarapu","year":"2008","journal-title":"Endocrinology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.tibs.2005.03.002","article-title":"The mammalian Mediator complex and its role in transcriptional regulation","volume":"30","author":"Conaway","year":"2005","journal-title":"Trends Biochem. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nature07829","article-title":"Histone modifications at human enhancers reflect global cell-type-specific gene expression","volume":"459","author":"Heintzman","year":"2009","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1101\/gr.078519.108","article-title":"Others Genome-wide relationship between histone H3 lysine 4 mono-and tri-methylation and transcription factor binding","volume":"18","author":"Robertson","year":"2008","journal-title":"Genome Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1126\/science.1067799","article-title":"Capturing Chromosome Conformation","volume":"295","author":"Dekker","year":"2002","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1210\/me.2009-0242","article-title":"Male-Specific Hepatic Bcl6: Growth Hormone-Induced Block of Transcription Elongation in Females and Binding to Target Genes Inversely Coordinated with STAT5","volume":"23","author":"Meyer","year":"2009","journal-title":"Mol. Endocrinol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3645","DOI":"10.1210\/en.2009-0212","article-title":"Computational and functional analysis of growth hormone (GH)-regulated genes identifies the transcriptional repressor B-cell lymphoma 6 (Bc16) as a participant in GH-regulated transcription","volume":"150","author":"Chen","year":"2009","journal-title":"Endocrinology"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Illingworth, R.S., Gruenewald-Schneider, U., Webb, S., Kerr, A.R.W., James, K.D., Turner, D.J., Smith, C., Harrison, D.J., Andrews, R., and Bird, A.P. (2010). Orphan CpG Islands Identify numerous conserved promoters in the mammalian genome. PLoS Genet., 6.","DOI":"10.1371\/journal.pgen.1001134"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/321209a0","article-title":"CpG-rich islands and the function of DNA methylation","volume":"321","author":"Bird","year":"1986","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nature01080","article-title":"Active genes are trimethylated at K4 of histone H3","volume":"419","author":"Schneider","year":"2002","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/35087620","article-title":"Rb targets histone H3 methylation and HP1 to promoters","volume":"412","author":"Nielsen","year":"2001","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1126\/science.1076997","article-title":"Role of histone H3 lysine 27 methylation in Polycomb-group silencing","volume":"298","author":"Cao","year":"2002","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s13148-016-0222-5","article-title":"Epigenetic drugs: From chemistry via biology to medicine and back","volume":"8","author":"Altucci","year":"2016","journal-title":"Clin. Epigenet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1126\/science.1063127","article-title":"Translating the Histone Code","volume":"293","author":"Jenuwein","year":"2001","journal-title":"Science"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.gde.2012.02.013","article-title":"Combinatorial complexity in chromatin structure and function: Revisiting the histone code","volume":"22","author":"Rando","year":"2012","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1096\/fj.14-258442","article-title":"Intrauterine growth restriction disrupts developmental epigenetics around distal growth hormone response elements on the rat hepatic IGF-1 gene","volume":"29","author":"Fu","year":"2015","journal-title":"FASEB J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7894","DOI":"10.1016\/S0021-9258(18)47652-1","article-title":"Mosaic evolution of the insulin-like growth factors. Organization, sequence, and expression of the rat insulin-like growth factor I gene","volume":"262","author":"Shimatsu","year":"1987","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"21505","DOI":"10.1016\/S0021-9258(19)36638-4","article-title":"Chromatin changes accompany the developmental activation of insulin-like growth factor I gene transcription","volume":"267","author":"Kikuchi","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3836","DOI":"10.1210\/endo.142.9.8400","article-title":"STAT5b is required for GH-induced liver Igf-I gene expression","volume":"142","author":"Davey","year":"2001","journal-title":"Endocrinology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"22696","DOI":"10.1074\/jbc.M301362200","article-title":"Acute Control of Insulin-like Growth Factor-I Gene Transcription by Growth Hormone through Stat5b *","volume":"278","author":"Papers","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nature05915","article-title":"The complex language of chromatin regulation during transcription","volume":"447","author":"Berger","year":"2007","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.cell.2007.05.009","article-title":"High-Resolution Profiling of Histone Methylations in the Human Genome","volume":"129","author":"Barski","year":"2007","journal-title":"Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"17732","DOI":"10.1074\/jbc.M500796200","article-title":"Spatial distribution of di- and tri-methyl lysine 36 of histone H3 at active genes","volume":"280","author":"Bannister","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1053\/j.semperi.2007.11.005","article-title":"Adult Sequelae of Intrauterine Growth Restriction","volume":"32","author":"Ross","year":"2008","journal-title":"Semin. Perinatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1515\/JPEM.2010.23.3.215","article-title":"Intrauterine Growth Restriction as a Potential Risk Factor for Disease Onset in Adulthood","volume":"23","author":"Varvarigou","year":"2010","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.1096\/fj.08-124768","article-title":"Epigenetics: Intrauterine growth retardation (IUGR) modifies the histone code along the rat hepatic IGF-1 gene","volume":"23","author":"Fu","year":"2009","journal-title":"FASEB J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/0092-8674(80)90237-8","article-title":"Cellular differentiation, cytidine analogs and DNA methylation","volume":"20","author":"Jones","year":"1980","journal-title":"Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1126\/science.1126100","article-title":"Pituitary adenoma predisposition caused by germline mutations in the AIP gene","volume":"312","author":"Vierimaa","year":"2006","journal-title":"Science"},{"key":"ref_58","first-page":"1262","article-title":"Loss of Expression of GADD45\u03b3, a Growth Inhibitory Gene, in Human Pituitary Adenomas: Implications for Tumorigenesis","volume":"87","author":"Zhang","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1158\/2159-8290.CD-11-0214","article-title":"Combination Epigenetic Therapy Has Efficacy in Patients with Refractory Advanced Non \u2013 Small Cell Lung Cancer","volume":"1","author":"Juergens","year":"2011","journal-title":"Cancer Discov."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1038\/leu.2008.397","article-title":"The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells","volume":"23","author":"Flotho","year":"2009","journal-title":"Leukemia"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.ccr.2004.08.029","article-title":"Distinct effects on gene expression of chemical and genetic manipulation of the cancer epigenome revealed by a multimodality approach","volume":"6","author":"Gius","year":"2004","journal-title":"Cancer Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/5047","article-title":"Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer","volume":"21","author":"Cameron","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"7811","DOI":"10.1073\/pnas.93.15.7811","article-title":"Minimal definition of the imprinting center and fixation of chromosome 15q11-q13 epigenotype by imprinting mutations","volume":"93","author":"Saitoh","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1093\/hmg\/10.6.645","article-title":"Association of acetylated histones with paternally expressed genes in the Prader--Willi deletion region","volume":"10","author":"Francke","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1086\/324469","article-title":"Parent-Specific Complementary Patterns of Histone H3 Lysine 9 and H3 Lysine 4 Methylation at the Prader-Willi Syndrome Imprinting Center","volume":"69","author":"Xin","year":"2001","journal-title":"AJHG"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nm.4257","article-title":"Targeting the histone methyltransferase G9a activates imprinted genes and improves survival of a mouse model of Prader\u2013Willi syndrome","volume":"23","author":"Kim","year":"2016","journal-title":"Nat. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1038\/nbt.2701","article-title":"Locus-specific editing of histone modifications at endogenous enhancers","volume":"31","author":"Mendenhall","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1007\/s40142-016-0104-3","article-title":"Epigenetic Editing: On the Verge of Reprogramming Gene Expression at Will","volume":"4","author":"Rots","year":"2016","journal-title":"Curr. Genet. Med. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/nrd.2016.175","article-title":"Screening out irrelevant cell-based models of disease","volume":"15","author":"Horvath","year":"2016","journal-title":"Nat. Rev. Drug Discov."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/10\/1624\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:46:37Z","timestamp":1760208397000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/10\/1624"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,5]]},"references-count":69,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2017,10]]}},"alternative-id":["ijms18101624"],"URL":"https:\/\/doi.org\/10.3390\/ijms18101624","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10,5]]}}}