{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:12:34Z","timestamp":1786479154731,"version":"build-2736575974"},"reference-count":141,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"crossref","award":["EP\/Y030818\/1"],"award-info":[{"award-number":["EP\/Y030818\/1"]}],"id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Retinoic acid receptor (RAR\u03b3) mRNA is expressed spatially and temporally during mouse embryogenesis and largely within stem and progenitor cells, indicating a role in organ formation. RAR\u03b3 agonism promoted the maintenance of hematopoietic stem cells, and blocked stem cell development as shown for hematopoiesis, zebrafish development, and chondrogenesis. Transgene expression enhanced the generation of induced pluripotent stem cells, indicating a role in ground-state pluripotency. RAR\u03b3 is oncogenic in acute myeloid leukemia, cholangiocarcinoma, and colorectal, head and neck, hepatocellular, ovarian, pancreatic, prostate, and renal cancers. RAR\u03b3 agonism or overexpression enhanced the proliferation of cancer cells. Conversely, antagonism or inhibition of all-trans retinoic acid synthesis led to the death of cancer cells including cancer stem cells. The pathways regulated by RAR\u03b3, via canonical activation and repression of gene expression, include Wnt\/\u03b2-catenin and Notch signaling. RAR\u03b3 also acts as a co-factor to Smad3 and reduced or enhanced TGF\u03b2-driven and Smad3-mediated events when liganded and non-liganded, respectively. Collectively the findings support the view that RAR\u03b3 plays a crucial role in controlling stem and progenitor cell behavior.<\/jats:p>","DOI":"10.3390\/ijms27031291","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T08:48:04Z","timestamp":1769590084000},"page":"1291","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Influences of RAR\u03b3 on the Behavior of Normal and Cancer Stem Cells"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0821-0275","authenticated-orcid":false,"given":"Geoffrey","family":"Brown","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, College of Medicine and Health, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/nm0797-730","article-title":"Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell","volume":"3","author":"Bonnet","year":"1997","journal-title":"Nat. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/s41392-024-01851-y","article-title":"Cancer stem cells: Advances in knowledge and implications for cancer therapy","volume":"9","author":"Chu","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1172\/JCI109193","article-title":"Chronic myelocytic leukemia: Origin of some lymphocytes from leukemic stem cell","volume":"62","author":"Fialkow","year":"1978","journal-title":"J. Clin. Investig."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1182\/blood.V99.1.319","article-title":"Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro","volume":"99","author":"Graham","year":"2002","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1172\/JCI35721","article-title":"Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity","volume":"121","author":"Corbin","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1200\/JCO.2009.21.8073","article-title":"Allogeneic hematopoietic stem-cell transplantation for patients 50 years or older with myelodysplastic syndromes or secondary acute myeloid leukemia","volume":"28","author":"Lim","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.pharmthera.2013.01.014","article-title":"Cancer stem cells and their role in metastasis","volume":"138","author":"Shiozawa","year":"2013","journal-title":"Pharmacol. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1210\/me.2008-0465","article-title":"Expression profiling of nuclear receptors in human and mouse embryonic stem cells","volume":"23","author":"Xie","year":"2009","journal-title":"Mol. Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.ccell.2017.10.002","article-title":"Acute promyelocytic leukemia: A paradigm for oncoprotein-targeted cure","volume":"32","author":"Pandolfi","year":"2017","journal-title":"Cancer Cell."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/978-3-031-62731-6_14","article-title":"Function of PML-RARA in acute promyelocytic leukemia","volume":"1459","author":"Testa","year":"2024","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1182\/blood.V101.4.1558","article-title":"Global down-regulation of HOX gene expression in PML-RARa+ acute promyelocytic leukemia identified by small-array real-time PCR","volume":"101","author":"Thompson","year":"2003","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/sj.leu.2404572","article-title":"A redundant potential of the retinoic receptor (RAR) a, b, and g isoforms in acute promyelocytic leukemia","volume":"21","author":"Marinelli","year":"2002","journal-title":"Leukemia"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Conserva, M.R., Redavid, I., Anelli, L., Zagaria, A., Specchia, G., and Albano, F. (2019). RARG gene dysregulation in acute myeloid leukemia. Front. Mol. Biosci., 6.","DOI":"10.3389\/fmolb.2019.00114"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/s41467-024-55047-7","article-title":"Oncogenic role of RARG rearrangements in acute myeloid leukemia resembling acute promyelocytic leukemia","volume":"16","author":"Wang","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/s41467-024-54860-4","article-title":"CPSF-6-RAR\u03b3 interacts with histone deacetylase 3 to promote myeloid transformation in RARG-fusion acute myeloid leukemia","volume":"16","author":"Liu","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Brown, G. (2023). Deregulation of all-trans retinoic acid signalling and development in cancer. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512089"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1146\/annurev-pathmechdis-031621-025610","article-title":"Cancer as a disease of development gone awry","volume":"19","author":"Stanger","year":"2023","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"107398","DOI":"10.1016\/j.pharmthera.2019.107398","article-title":"Environmental exposures, stem cells, and cancer","volume":"204","author":"Thong","year":"2019","journal-title":"Pharmacol. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e264","DOI":"10.1002\/wdev.264","article-title":"News insights and challenging paradigms in the regulation of vitamin A metabolism in development","volume":"6","author":"Shannan","year":"2017","journal-title":"Wiley Interdiscip. Rep. Dev. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"T13","DOI":"10.1530\/JME-22-0097","article-title":"Retinoic acid receptors at 35 years","volume":"69","author":"Petkovich","year":"2022","journal-title":"J. Mol. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1111\/j.1440-169x.2004.00765.x","article-title":"All-trans retinoic acid enhances differentiation and influences permeability of intestinal Caco-2 cells under serum free conditions","volume":"46","author":"Baltes","year":"2004","journal-title":"Dev. Growth Differ."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s00005-016-0411-0","article-title":"Antagonising retinoic acid receptors increases myeloid cell production by cultured hematopoietic stem cells","volume":"65","author":"Brown","year":"2017","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"31491","DOI":"10.1074\/jbc.M205016200","article-title":"Activation of retinoic acid receptor-dependent transcription by all-trans-retinoic acid metabolites and isomers","volume":"277","author":"Idres","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1210\/me.2002-0340","article-title":"Retinoic acid receptors b and g do not repress, but instead activate target gene transcription in both the absence and presence of hormone ligand","volume":"17","author":"Hawksdottir","year":"2003","journal-title":"Mol. Endocrinol."},{"key":"ref_25","first-page":"2976","article-title":"RAR72 expression is regulated through a retinoic acid response element embedded in Sp1 sites","volume":"12","author":"Lehmann","year":"1992","journal-title":"Mol. Cell. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1002\/stem.479","article-title":"Retinoic acid synthesis promotes development of neural progenitors from mouse embryonic stem cells by suppressing endogenous Wnt-dependent nodal signaling","volume":"28","author":"Engberg","year":"2010","journal-title":"Stem Cells"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6197","DOI":"10.1073\/pnas.93.12.6197","article-title":"Cell-type and promoter-context dependent retinoic acid receptor (RAR) redundancies for RARbeta2 and Hoxa-1 activation in F9 and P19 cells can be artefactually generated by gene knockouts","volume":"93","author":"Taneja","year":"1996","journal-title":"Proc Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1046\/j.1523-1747.2002.01816.x","article-title":"High albumin levels restrict the kinetics of 13-cis retonic acid uptake and intracellular isomerization into all-trans retinoic acid and inhibit its anti-proliferative effect on SZ95 sebocytes","volume":"119","author":"Tsukada","year":"2002","journal-title":"J. Investig. Dermatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.ejmech.2011.12.002","article-title":"Binding sites of retinol and retinoic acid with serum albumins","volume":"48","author":"Belatik","year":"2012","journal-title":"Eur. J. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/bs.mie.2020.02.010","article-title":"Analysis of vitamin A and retinoids in biological matrices","volume":"637","author":"Czuba","year":"2020","journal-title":"Methods Enzymol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/jcb.20579","article-title":"Retinoid-mediated stimulation of steroid sulfatase activity in myeloid leukemic cell lines requires RARa and RXR and involves the phosphinositide 3-kinase and ERK-MAP kinase pathways","volume":"97","author":"Hughes","year":"2006","journal-title":"J. Cell. Biochem."},{"key":"ref_32","first-page":"410","article-title":"Treatment of HL60 cells with various combinations of retinoids and 1 alpha, 25 dihydroxyvitamin D3 results in differentiation towards neutrophils or monocytes or a failure to differentiate and apoptosis","volume":"9","author":"Bunce","year":"1995","journal-title":"Leukemia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/1756-8722-4-20","article-title":"Retinoic acid induces HL-60 differentiation via the upregulation of miR-663","volume":"4","author":"Jian","year":"2011","journal-title":"J. Hematol. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1182\/blood.V70.5.1233.1233","article-title":"The HL-60 promyelocytic leukaemic cell line: Proliferation, differentiation, and cellular oncogene expression","volume":"70","author":"Collins","year":"1987","journal-title":"Blood"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Glaser, T., La Banca de Oliveira, S., Cheffer, A., Beco, R., Martins, P., Fornazari, M., Lameu, C., Junior, H.M.C., and Coutino-Silva, R. (2014). Modulation of mouse embryonic stem cell proliferation and neural differentiation by the PZX7 receptor. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0096281"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1002\/ar.20686","article-title":"pCREB is involved in neural induction of mouse embryonic stem cells","volume":"291","author":"Shan","year":"2008","journal-title":"Anat. Rec."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1242\/dev.065938","article-title":"Retinoic acid signalling during development","volume":"139","author":"Rhinn","year":"2012","journal-title":"Development"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"55","DOI":"10.3109\/15569548609012706","article-title":"Toxicity of retinoids in humans and animals","volume":"5","author":"Howard","year":"1986","journal-title":"J. Toxicol. Toxin Rev."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Hudhud, L., Chisholm, D.R., Whiting, A., Steib, A., Pohoczky, K., Kecskes, A., Szoke, E., and Helyes, Z. (2022). Synthetic diphenylacetylene-based retinoids induce DNA damage in Chinese hamster ovary cells without altering viability. Molecules, 27.","DOI":"10.3390\/molecules27030977"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1002\/bdra.20712","article-title":"Genetic and pathological aspects of retinoic acid-induced limb malformations in the mouse","volume":"88","author":"Lee","year":"2010","journal-title":"Birth Defects Res. A Clin. Mol. Teratol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1093\/jn\/131.3.705","article-title":"Function of vitamin A in vertebrate embryonic development","volume":"131","year":"2001","journal-title":"J. Nutr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.1242\/dev.120.10.2723","article-title":"Function of retinoic acid receptors (RARs) during development: (1) craniofacial and skeletal abnormities in RAR double mutants","volume":"120","author":"Lohnes","year":"1994","journal-title":"Development"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1242\/dev.108.2.213","article-title":"Specific spatial and temporal distribution of retinoic acid receptor gamma transcripts during mouse embryogenesis","volume":"108","author":"Ruberte","year":"1990","journal-title":"Development"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1002\/dvdy.21049","article-title":"Comparison of the expression patterns of newly identified zebrafish retinoic acid and retinoid X receptors","volume":"236","author":"Waxman","year":"2007","journal-title":"Dev. Dyn."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.modgep.2005.10.007","article-title":"Characterization of the retinoic acid receptor genes raraa, rarab and rarg during zebrafish development","volume":"6","author":"Hale","year":"2006","journal-title":"Gene Expr. Patterns"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/1523-1747.ep12469889","article-title":"Retinoic acid receptor expression in human skin","volume":"96","author":"Elder","year":"1991","journal-title":"J. Investig. Dermatol."},{"key":"ref_47","first-page":"1463","article-title":"Cellular localization of retinoic acid receptor-\u03b3 expression in normal and neoplastic skin","volume":"140","author":"Finzi","year":"1992","journal-title":"Am. J. Pathol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Gericke, J., Ittensohn, J., Mihaly, J., Alvarez, S., Alvarez, R., Torocsik, D., de Lera, A., and Ruhl, R. (2013). Regulation of retinoid-mediated signaling involved in skin homeostasis by RAR and RXR agonists\/antagonists in mouse skin. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0062643"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1084\/jem.20052105","article-title":"RAR\u03b3 is critical for maintaining a balance between hematopoietic stem cell self-renewal and differentiation","volume":"203","author":"Purton","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"7178","DOI":"10.1038\/sj.onc.1204757","article-title":"Function of RAR\u03b1 during the maturation of neutrophils","volume":"20","author":"Kastner","year":"2001","journal-title":"Oncogene"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1182\/blood.V98.8.2563","article-title":"Lineage restriction of the RARalpha gene expression in myeloid differentiation","volume":"98","author":"Zhu","year":"2001","journal-title":"Blood"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1189\/jlb.1211609","article-title":"The granulocyte-colony stimulating factor receptor (G-CSFR) interacts with retinoic acid receptors (RARs) in the regulation of myeloid differentiation","volume":"93","author":"Chee","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/s41590-021-00925-1","article-title":"A latent subset of hematopoietic stem cells resists regenerative stress to preserve stemness","volume":"22","author":"Kaufmann","year":"2021","journal-title":"Nat. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/j.celrep.2018.10.021","article-title":"Integrated stress response activity marks stem cells in normal haematopoiesis and leukemia","volume":"25","author":"Mbong","year":"2018","journal-title":"Cell Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3911","DOI":"10.1182\/blood-2003-10-3688","article-title":"Retinoic acid regulates C\/EBP homologous protein expression (CHOP), which negatively regulates myeloid target genes","volume":"104","author":"Gery","year":"2004","journal-title":"Blood"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Melis, M., Trasino, S.E., Tang, X.-H., Rappa, A., Zhang, T., Qin, L., and Gudas, L.J. (2023). Retinoic acid receptor \u03b2 loss in hepatocytes increases steatosis and elevates the integrated stress response in alcohol-associated liver disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512035"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Neill, G., and Masson, G.R. (2023). A stay of execution: ATF4 regulation and potential outcomes for the integrated stress response. Front. Mol. Neurosci., 16.","DOI":"10.3389\/fnmol.2023.1112253"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1089\/scd.2014.0235","article-title":"The development and growth of tissues derived from cranial neural crest and primitive mesoderm is dependent on the ligation status of retinoic acid receptor \u03b3: Evidence that retinoic acid receptor \u03b3 functions to maintain stem\/progenitors in the absence of retinoic acid","volume":"24","author":"Wai","year":"2015","journal-title":"Stem Cells Dev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1534\/genetics.119.302345","article-title":"Fibroblast growth factor receptors function redundantly during zebrafish development","volume":"212","author":"Leerberg","year":"2019","journal-title":"Genetics"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.ydbio.2008.06.033","article-title":"Reiterative roles for FGF signaling in the establishment of size and proportion of the zebrafish heart","volume":"321","author":"Marques","year":"2008","journal-title":"Dev. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/nm.2334","article-title":"Potent inhibition of heterotopic ossification by nuclear receptor-\u03b3 agonists","volume":"17","author":"Shimono","year":"2011","journal-title":"Nat. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2260","DOI":"10.1242\/dev.103705","article-title":"Active repression by RAR\u03b3 signalling is required for vertebrate axial elongation","volume":"141","author":"Janesick","year":"2014","journal-title":"Development"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"18283","DOI":"10.1073\/pnas.1100893108","article-title":"Rapid and efficient reprogramming of somatic cells into induced pluripotent stem cells by retonic acid receptor gamma and liver receptor homolog 1","volume":"108","author":"Wang","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1002\/stem.1926","article-title":"Signalling through retinoic acid receptors is required for reprogramming of both mouse embryonic fibroblast cells and epiblast stem cells to induced pluripotent stem cells","volume":"33","author":"Yang","year":"2015","journal-title":"Stem Cells"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.gendis.2023.01.030","article-title":"Canonical and noncanonical Wnt signalling: Multilayered mediators, signalling mechanisms and major signalling crosstalk","volume":"11","author":"Qin","year":"2024","journal-title":"Genes Dis."},{"key":"ref_66","first-page":"683","article-title":"Regulation of WNT signalling molecules by retinoic acid during neuronal differentiation of NT2 cells: The threshold model of WNT action","volume":"10","author":"Katoh","year":"2002","journal-title":"Int. J. Mol. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e898","DOI":"10.1038\/cddis.2013.424","article-title":"Retinoic acid alters the proliferation and survival of the epithelium and mesenchyme and suppresses Wnt\/\u03b2-catenin signalling in the developing cleft palate","volume":"4","author":"Hu","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2589","DOI":"10.1016\/j.stemcr.2021.09.010","article-title":"Retinoic acid signaling in heart development: Application in the differentiation of cardiovascular lineages from human pluripotent stem cells","volume":"16","author":"Wiesinger","year":"2012","journal-title":"Stem Cell Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1186\/s13287-022-03006-8","article-title":"RA signalling pathway combined with Wnt signalling pathway regulates human induced pluripotent stem cells (hiPSCs) differentiation to sinus node-like cells","volume":"13","author":"Yin","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"EMBR2018475332020","DOI":"10.15252\/embr.201847533","article-title":"Temporal activation of LRH-1 and RAR-g in human pluripotent stem cells induces a functional na\u00efve-like state","volume":"21","author":"Taei","year":"2020","journal-title":"EMBO Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"a022186","DOI":"10.1101\/cshperspect.a022186","article-title":"TGF-\u03b2 family signaling in embryonic and somatic stem-cell renewal and differentiation","volume":"9","author":"Mullen","year":"2017","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.semnephrol.2012.04.008","article-title":"Retinoic and TGF\u03b2 families: Crosstalk in development, neoplasia, immunity and tissue repair","volume":"32","author":"Xu","year":"2012","journal-title":"Semin. Nephrol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/nature05950","article-title":"Derivation of pluripotent epiblast stem cells from mammalian embryos","volume":"448","author":"Brons","year":"2007","journal-title":"Nature"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1242\/dev.01706","article-title":"TGF\u03b2\/activin\/nodal signalling is necessary for the maintenance of pluripotency in human embryonic stem cells","volume":"132","author":"James","year":"2005","journal-title":"Development"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1242\/dev.033951","article-title":"Activin\/Nodal signalling maintains pluripotency by controlling Nanog expression","volume":"136","author":"Vallier","year":"2009","journal-title":"Development"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e67259","DOI":"10.7554\/eLife.67259","article-title":"TGF\u03b2 is required to maintain pluripotency of human na\u00efve pluripotent stem cells","volume":"10","author":"Osnato","year":"2012","journal-title":"eLife"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.cell.2008.07.001","article-title":"TGF\u03b2 in cancer","volume":"134","author":"Massague","year":"2008","journal-title":"Cell"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1016\/j.celrep.2016.02.036","article-title":"YAP induces human naive pluripotency","volume":"14","author":"Qin","year":"2016","journal-title":"Cell. Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"823","DOI":"10.4161\/epi.21141","article-title":"Judge, jury and executioner of stem cell fate","volume":"7","author":"Tollervey","year":"2012","journal-title":"Epigenetics"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3250","DOI":"10.1074\/jbc.M110.157545","article-title":"Epigenetic reorganization of the clustered Hox genes in embryonic stem cells induced by retinoic acid","volume":"286","author":"Kashyap","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_81","first-page":"999","article-title":"RAR\u03b3 is essential for retinoic acid induced chromatin remodelling and transcriptional activation in embryonic stem cells","volume":"126","author":"Kashyap","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"4833","DOI":"10.1093\/nar\/gkv370","article-title":"RAR\/RXR binding dynamics distinguish pluripotency from differentiation associated cis-regulatory elements","volume":"43","author":"Chatagnon","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1006\/dbio.1999.9207","article-title":"Retinoid signalling is required for chondrocyte maturation and endochondral bone formation","volume":"208","author":"Koyama","year":"1999","journal-title":"Dev. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.ydbio.2009.01.031","article-title":"Retinoic acid receptors are required for skeletal growth, matrix homeostasis and growth plate function in postnatal mouse","volume":"328","author":"Williams","year":"2009","journal-title":"Dev. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1074\/jbc.M109.053926","article-title":"Wnt\/\u03b2-catenin and retinoic acid receptor signaling pathways interact to regulate chondrocyte function and matrix turnover","volume":"285","author":"Yasuhara","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"8212","DOI":"10.1038\/sj.onc.1206913","article-title":"Retinoic acid receptors interfere with TGF-\u03b2\/Smad signaling pathway in a ligand-specific manner","volume":"22","author":"Pendaries","year":"2003","journal-title":"Oncogene"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1038\/s41598-017-00233-5","article-title":"Targeting to the non-genomic activity of retinoic acid receptor-gamma by acacetin in hepatocellular carcinoma","volume":"7","author":"Zeng","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"11534","DOI":"10.1016\/S0021-9258(19)50233-2","article-title":"Dimerization interfaces of thyroid hormone, retinoic acid, vitamin D, and retinoid X receptors","volume":"268","author":"Rosen","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/0092-8674(89)90016-0","article-title":"Positive and negative regulation of gene transcription by a retinoic acid-thyroid hormone receptor heterodimer","volume":"59","author":"Glass","year":"1989","journal-title":"Cell"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"23248","DOI":"10.1016\/S0021-9258(18)50083-1","article-title":"Triiodothyronine (T3) differentially affects T3-receptor\/retinoic acid receptor and T3-receptor\/retinoid X receptor heterodimer binding to DNA","volume":"267","author":"Yen","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1089\/dna.1994.13.333","article-title":"Thyroid hormone and retinoic acid receptors form heterodimers with retinoid X receptors on direct repeats, palindromes, and inverted palindromes","volume":"13","author":"Schrader","year":"1994","journal-title":"DNA Cell Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1210\/me.2004-0210","article-title":"Heterodimers of retinoic acid receptors and thyroid hormone receptors display unique combinatorial regulatory properties","volume":"19","author":"Lee","year":"2005","journal-title":"Mol. Endocrinol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1186\/s13287-022-02799-y","article-title":"Thyroid hormone enhances stem cell maintenance and promotes lineage-specific differentiation in human embryonic stem cells","volume":"13","author":"Deng","year":"2002","journal-title":"Stem Cell Res. Ther."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1182\/blood-2007-07-102798","article-title":"Acute promyelocytic leukemia: From highly fatal to highly curable","volume":"111","author":"Wang","year":"2008","journal-title":"Blood"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Watts, J.M., Perez, A., Pereira, L., Fan, Y.-S., Brown, G., Vega, F., Petrie, K., Swords, R.T., and Zelent, A. (2017). A case of AML characterized by a novel t (4; 15) (q31; q22) translocation that confers a growth-stimulatory response to retinoid-based therapy. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071492"},{"key":"ref_96","first-page":"e1284","article-title":"Retinoic acid receptor \u03b3 is a therapeutically targetable drive of growth and survival in prostate cancer","volume":"3","author":"Petrie","year":"2020","journal-title":"Cancer Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7150\/ijbs.100351","article-title":"Oncogenic RAR\u03b3 isoforms promote head and neck cancer proliferation through vinexin-b-mediated cell cycle acceleration and autocrine activation of EGFR signal","volume":"21","author":"Su","year":"2025","journal-title":"Int. J. Biol. Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1158\/0008-5472.CAN-09-2968","article-title":"Oncogenic potential of retinoic acid receptor-\u03b3 in hepatocellular carcinoma","volume":"70","author":"Yan","year":"2010","journal-title":"Cancer Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3416","DOI":"10.1128\/MCB.00384-13","article-title":"Oncogenic activity of the retinoic acid receptor \u03b3 is exhibited through activation of the Akt\/NF-\u03baB and Wnt\/\u03b2-catenin pathways in cholangiocarcinoma","volume":"33","author":"Huang","year":"2013","journal-title":"Mol. Cell. Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1080\/15384101.2017.1295180","article-title":"Oncogenic retinoic acid receptor \u03b3 knockdown reverses multidrug resistance of human colorectal cancer via Wnt\/\u03b2-catenin pathway","volume":"16","author":"Huang","year":"2017","journal-title":"Cell Cycle"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Cizmarikova, M., Michalkova, R., Franko, O., Leskova, B., Homolya, A.D., Gabzdilova, J., and Takac, P. (2025). Targeting multidrug resistance in cancer: Impact of retinoids, rexinoids, and carotinoids on ABC transporters. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262211157"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Xiu, L., Zhao, Y., Li, N., Zeng, J., Liu, J., Fu, Y., Gao, Q., and Wu, L. (2022). High expression of RARG accelerates ovarian cancer progression by regulating cell proliferation. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1063031"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1002\/cbin.11917","article-title":"Retinoic acid receptor gamma is required for proliferation of pancreatic cancer cells","volume":"47","author":"Ji","year":"2023","journal-title":"Cell Biol. Int."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s12935-023-02928-4","article-title":"Blockage of retinoic acid signalling via RARgamma suppressed the proliferation of pancreatic cancer cells by arresting the cell cycle progression in G1-S phase","volume":"23","author":"Yamakowa","year":"2023","journal-title":"Cancer Cell Int."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1002\/j.1939-4640.2002.tb02341.x","article-title":"Immunological localization of the retinoic acid receptors in human prostate","volume":"23","author":"Richter","year":"2002","journal-title":"J. Androl."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"5350","DOI":"10.1038\/sj.onc.1207682","article-title":"RARg acts as a tumor suppressor in mouse keratinocytes","volume":"23","author":"Chen","year":"2004","journal-title":"Oncogene"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.isci.2019.06.019","article-title":"Retinoic acid receptor-g in DNA damage induced necroptosis","volume":"17","author":"Kadgamuwa","year":"2019","journal-title":"iScience"},{"key":"ref_108","first-page":"110905","article-title":"Multiple modes of transcription regulation by the nuclear hormone receptor RAR\u03b3 in human squamous cell carcinoma","volume":"302","author":"Hoxie","year":"2025","journal-title":"J. Biol. Chem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"559","DOI":"10.18632\/oncotarget.512","article-title":"Solid tumor differentiation therapy\u2014Is it possible?","volume":"3","author":"Cruz","year":"2012","journal-title":"Oncotarget"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1002\/(SICI)1097-4652(199906)179:3<336::AID-JCP11>3.0.CO;2-Q","article-title":"Activation of Rb and decline in androgen receptor protein precede retinoic acid induced apoptosis in androgen-dependent LNCaP cells and their androgen-independent derivative","volume":"179","author":"Gao","year":"1999","journal-title":"J. Cell. Physiol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1054\/bjoc.2001.1939","article-title":"Antagonists of retinoic acid receptors (RARs) are potent growth inhibitors of prostate carcinoma cells","volume":"85","author":"Hammond","year":"2001","journal-title":"Br. J. Cancer"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1002\/(SICI)1097-0215(19990118)80:2<272::AID-IJC17>3.0.CO;2-X","article-title":"A selective retinoid with high activity against an androgen-resistant prostate cancer cell type","volume":"80","author":"Lu","year":"1999","journal-title":"Int. J. Cancer"},{"key":"ref_113","first-page":"2186","article-title":"Abnormal level of retinoic acid in prostate cancer tissues","volume":"81","author":"Pasquali","year":"1996","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1002\/mc.22158","article-title":"Reduced retinoids and retinoid receptors\u2019 expression in pancreatic cancer: A link to patient survival","volume":"54","author":"Bleul","year":"2015","journal-title":"Mol. Carcinog."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.ygyno.2008.11.015","article-title":"Vitamin A metabolism is impaired in human ovarian cancer","volume":"112","author":"Williams","year":"2009","journal-title":"Gynecol. Oncol."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Choi, J.-A., Kwan, H., Cho, H., Chung, J.-Y., Hewitt, S.M., and Kim, J.-H. (2019). ALDH1A2 is a candidate tumor suppressor gene in ovarian cancer. Cancer, 11.","DOI":"10.3390\/cancers11101553"},{"key":"ref_117","first-page":"317","article-title":"Expression of genes involved in retinoic acid biosynthesis in human gastric cancer","volume":"47","author":"Kroptova","year":"2013","journal-title":"Mol. Biol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1134\/S0026893316020138","article-title":"Abnormal expression of genes that regulate retinoid metabolism in non-small-cell lung cancer","volume":"50","author":"Kuznetsova","year":"2016","journal-title":"Mol. Biol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1186\/s12943-015-0476-0","article-title":"Impaired aldehyde dehydrogenase subfamily member 2A-dependent retinoic acid signaling is related with a mesenchymal-like phenotype and an unfavourable prognosis of head and neck squamous cell carcinoma","volume":"14","author":"Seidensaal","year":"2015","journal-title":"Mol. Cancer"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"967","DOI":"10.13005\/bpj\/1036","article-title":"Upregulation of Rarb, Rarg, and Rorc Genes in Clear Cell Renal Cell Carcinoma","volume":"9","author":"Kudryavtseva","year":"2016","journal-title":"Biomed. Pharmacol. J."},{"key":"ref_121","first-page":"2774","article-title":"Reduced levels of retinyl esters and vitamin A in human renal cancers","volume":"61","author":"Guo","year":"2001","journal-title":"Cancer Res."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Brown, G., and Petrie, K. (2021). The RAR\u03b3 oncogene: An Achilles heel for some cancers. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073632"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/biof.5520130117","article-title":"Carotenoids and retinoids as suppressors on adipocyte differentiation via nuclear receptors","volume":"13","author":"Kawada","year":"2000","journal-title":"Biofactors"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"112","DOI":"10.2337\/db11-1620","article-title":"Retinoic acid upregulates preadipocyte genes to block adipogenesis and suppress diet-induced obesity","volume":"61","author":"Berry","year":"2012","journal-title":"Diabetes"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1158\/1078-0432.CCR-10-2523","article-title":"Human prostate cancer harbors the stem cell properties of bone marrow mesenchymal stem cells","volume":"17","author":"Zhau","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1038\/s41419-019-2172-2","article-title":"All trans retinoic acid enhances, and a pan-RAR antagonist counteracts, the stem cell promoting activity of EV11 in acute myeloid leukemia","volume":"10","author":"Nguyan","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"3061","DOI":"10.1016\/j.celrep.2019.02.032","article-title":"A pan-ALDH1A inhibitor induces necroptosis in ovarian cancer stem-like cells","volume":"26","author":"Chefetz","year":"2019","journal-title":"Cell Rep."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2756","DOI":"10.1038\/s41388-020-1184-9","article-title":"Dual disruption of aldehyde dehydrogenases 1 and 3 promotes functional changes in the glutathione redox system and enhances chemosensitivity in non-small cell lung cancer","volume":"39","author":"Venton","year":"2020","journal-title":"Oncogene"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.stemcr.2019.08.015","article-title":"ALDH-dependent glycolytic activation mediates stemness and paclitaxel resistance in patient-derived spheroid models of uterine endometrial cancer","volume":"13","author":"Mori","year":"2019","journal-title":"Stem Cell Rep."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Jiang, Y., Song, H., Jiang, L., Qiao, Y., Yang, D., Wang, D., and Li, J. (2020). Silybin prevents prostate cancer by inhibited the ALDH1A1 expression in the retinol metabolism pathway. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.574394"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.7150\/jca.12738","article-title":"Solanum incanum extract downregulates aldehyde dehydrogenase 1-mediated stemness and inhibits tumor formation in ovarian cancer cells","volume":"6","author":"Wu","year":"2015","journal-title":"J. Cancer"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.3390\/nu6031209","article-title":"Vitamin A\/retinol and the maintenance of pluripotency of stem cells","volume":"6","author":"Khillan","year":"2014","journal-title":"Nutrients"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/stem.251","article-title":"A novel signaling by vitamin a\/retinol promotes self-renewal of mouse embryonic stem cells by activating PI3K\/Akt signaling pathway via insulin-like growth factor-1 receptor","volume":"28","author":"Chen","year":"2010","journal-title":"Stem Cells"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"3123","DOI":"10.1016\/j.febslet.2010.05.052","article-title":"Activation of retinoic acid receptor signalling coordinates lineage commitment of spontaneously differentiating mouse embryonic stem cells in embryoid bodies","volume":"584","author":"Simandi","year":"2010","journal-title":"FEBS Lett."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/j.cell.2008.09.002","article-title":"Retinoic acid synthesis and signalling during early organogenesis","volume":"19","author":"Duester","year":"2008","journal-title":"Cell"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/msb.2011.73","article-title":"Dissecting the retinoid-induced differentiation of F9 embryonal stem cells by integrative genomics","volume":"7","author":"Walia","year":"2011","journal-title":"Mol. Syst. Biol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"18503","DOI":"10.1074\/jbc.M109.007708","article-title":"A unique cytoplasmic localization of retinoic acid receptor-g and its regulations","volume":"284","author":"Han","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"043007","DOI":"10.1103\/dkmq-h4d9","article-title":"Mathematical framework for hierarchical cell identity controlling collective enhancer dynamics","volume":"3","author":"Grishechkin","year":"2025","journal-title":"PRX Life"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1210\/en.2010-0941","article-title":"Oral administration of a retinoic receptor antagonist reversibly inhibits spermatogenesis in mice","volume":"152","author":"Chung","year":"2011","journal-title":"Endocrinology"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1093\/toxsci\/59.2.297","article-title":"BMS-189453, a novel retinoid receptor antagonist, is a potent testicular toxin","volume":"59","author":"Schulze","year":"2001","journal-title":"Toxicol. Sci."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"e469","DOI":"10.1038\/bcj.2016.78","article-title":"Aldehyde dehydrogenases inhibition eradicated leukaemia stem cells while sparing normal progenitors","volume":"6","author":"Venton","year":"2016","journal-title":"Blood Cancer J."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1291\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T05:15:16Z","timestamp":1769750116000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1291"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,28]]},"references-count":141,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["ijms27031291"],"URL":"https:\/\/doi.org\/10.3390\/ijms27031291","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,28]]}}}