{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T12:50:00Z","timestamp":1784033400854,"version":"3.55.0"},"reference-count":97,"publisher":"Georg Thieme Verlag KG","issue":"03","funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["R01 DK98414"],"award-info":[{"award-number":["R01 DK98414"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Liver Dis"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:p>Liver cancer is the sixth most common cancer and the fourth leading cause of cancer-related deaths worldwide. Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer and the incidence of HCC is on the rise. Liver cancers in general and HCC in particular do not respond to chemotherapy. Radiological ablation, surgical resection, and liver transplantation are the only medical therapies currently available. Hepatocyte nuclear factor 4 \u03b1 (HNF4\u03b1) is an orphan nuclear receptor expressed only in hepatocytes in the liver. HNF4\u03b1 is considered the master regulator of hepatic differentiation because it regulates a significant number of genes involved in various liver-specific functions. In addition to maintaining hepatic differentiation, HNF4\u03b1 also acts as a tumor suppressor by inhibiting hepatocyte proliferation by suppressing the expression of promitogenic genes and inhibiting epithelial to mesenchymal transition in hepatocytes. Loss of HNF4\u03b1 expression and function is associated with rapid progression of chronic liver diseases that ultimately lead to liver cirrhosis and HCC, including metabolism-associated steatohepatitis, alcohol-associated liver disease, and hepatitis virus infection. This review summarizes the role of HNF4\u03b1 in liver cancer pathogenesis and highlights its potential as a potential therapeutic target for HCC.<\/jats:p>","DOI":"10.1055\/a-2349-7236","type":"journal-article","created":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T22:52:15Z","timestamp":1718923935000},"page":"383-393","source":"Crossref","is-referenced-by-count":8,"title":["Role of Hepatocyte Nuclear Factor 4 Alpha in Liver Cancer"],"prefix":"10.1055","volume":"44","author":[{"given":"Manasi","family":"Kotulkar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Paine-Cabrera","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udayan","family":"Apte","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2024,7,16]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1101\/gad.4.12b.2353","article-title":"Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily","volume":"4","author":"F M Sladek","year":"1990","journal-title":"Genes Dev"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1478-1336-1-5","article-title":"Expression and localization of P1 promoter-driven hepatocyte nuclear factor-4\u03b1 (HNF4\u03b1) isoforms in human and rats","volume":"1","author":"S Jiang","year":"2003","journal-title":"Nucl 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Huck","year":"2019","journal-title":"Hepatology"},{"issue":"02","key":"ref9","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1055\/a-2097-0660","article-title":"HNF 4\u03b1 alpha in hepatocyte health and disease","volume":"43","author":"M Kotulkar","year":"2023","journal-title":"Semin Liver Dis"},{"issue":"02","key":"ref10","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1002\/hep.32326","article-title":"Progressive loss of hepatocyte nuclear factor 4 alpha activity in chronic liver diseases in humans","volume":"76","author":"S Gunewardena","year":"2022","journal-title":"Hepatology"},{"issue":"02","key":"ref11","doi-asserted-by":"crossref","first-page":"355","DOI":"10.3350\/cmh.2023.0070","article-title":"The latest global burden of liver cancer: a past and present threat","volume":"29","author":"J H Oh","year":"2023","journal-title":"Clin Mol 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Pathol"},{"issue":"02","key":"ref17","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3322\/canjclin.55.2.74","article-title":"Global cancer statistics, 2002","volume":"55","author":"D M Parkin","year":"2005","journal-title":"CA Cancer J Clin"},{"issue":"05","key":"ref18","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.jhep.2016.05.035","article-title":"Genetic profiling of hepatocellular carcinoma using next-generation sequencing","volume":"65","author":"K Schulze","year":"2016","journal-title":"J Hepatol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4103\/jcar.JCar_9_16","article-title":"Review of hepatocellular carcinoma: epidemiology, etiology, and carcinogenesis","volume":"16","author":"Y A Ghouri","year":"2017","journal-title":"J Carcinog"},{"issue":"16","key":"ref20","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1097\/QAD.0b013e32831103ad","article-title":"Influence of HIV-related immunodeficiency on the risk of 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Sci"},{"issue":"24","key":"ref43","doi-asserted-by":"crossref","first-page":"4330","DOI":"10.3748\/wjg.v23.i24.4330","article-title":"Implication of the Hedgehog pathway in hepatocellular carcinoma","volume":"23","author":"C M Della Corte","year":"2017","journal-title":"World J Gastroenterol"},{"issue":"04","key":"ref44","doi-asserted-by":"crossref","first-page":"742","DOI":"10.3350\/cmh.2020.0178","article-title":"Hepatic Hippo signaling inhibits development of hepatocellular carcinoma","volume":"26","author":"Y Liu","year":"2020","journal-title":"Clin Mol Hepatol"},{"issue":"05","key":"ref45","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/j.jhep.2020.01.019","article-title":"The landscape of gene mutations in cirrhosis and hepatocellular carcinoma","volume":"72","author":"M M\u00fcller","year":"2020","journal-title":"J Hepatol"},{"issue":"19","key":"ref46","doi-asserted-by":"crossref","first-page":"3557","DOI":"10.7150\/jca.26350","article-title":"The role of MicroRNAs in hepatocellular carcinoma","volume":"9","author":"X Xu","year":"2018","journal-title":"J Cancer"},{"issue":"01","key":"ref47","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1124\/jpet.111.179390","article-title":"Increased activation of the Wnt\/\u03b2-catenin pathway in spontaneous hepatocellular carcinoma observed in farnesoid X receptor knockout mice","volume":"338","author":"A Wolfe","year":"2011","journal-title":"J Pharmacol Exp Ther"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1146\/annurev-pharmtox-010715-103209","article-title":"Nuclear receptors as therapeutic targets in liver disease: are we there yet?","volume":"56","author":"S Rudraiah","year":"2016","journal-title":"Annu Rev Pharmacol Toxicol"},{"issue":"06","key":"ref49","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1210\/me.2004-0520","article-title":"Xenobiotic stress induces hepatomegaly and liver tumors via the nuclear receptor constitutive androstane 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Boyault","year":"2007","journal-title":"Hepatology"},{"issue":"01","key":"ref53","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41572-020-00240-3","article-title":"Hepatocellular carcinoma","volume":"7","author":"J M Llovet","year":"2021","journal-title":"Nat Rev Dis Primers"},{"issue":"17","key":"ref54","doi-asserted-by":"crossref","first-page":"3156","DOI":"10.4161\/cc.21721","article-title":"The yin and yang of proliferation and differentiation: cyclin D1 inhibits differentiation factors ChREBP and HNF4\u03b1","volume":"11","author":"F M Sladek","year":"2012","journal-title":"Cell Cycle"},{"issue":"01","key":"ref55","doi-asserted-by":"crossref","first-page":"2","DOI":"10.2133\/dmpk.23.2","article-title":"Regulation of hepatocyte nuclear factor 4 alpha-mediated transcription","volume":"23","author":"F J Gonzalez","year":"2008","journal-title":"Drug Metab Pharmacokinet"},{"issue":"03","key":"ref56","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3727\/105221615X14181438356292","article-title":"Role of hepatocyte nuclear factor 4\u03b1 (HNF4\u03b1) in cell proliferation and cancer","volume":"16","author":"C Walesky","year":"2015","journal-title":"Gene Expr"},{"issue":"19","key":"ref57","doi-asserted-by":"crossref","first-page":"7640","DOI":"10.1158\/0008-5472.CAN-10-0824","article-title":"Hepatocyte nuclear factor 4 alpha suppresses the development of hepatocellular carcinoma","volume":"70","author":"B F Ning","year":"2010","journal-title":"Cancer Res"},{"issue":"05","key":"ref58","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1002\/hep.22510","article-title":"Differentiation therapy of hepatocellular carcinoma in mice with recombinant adenovirus carrying hepatocyte nuclear factor-4alpha gene","volume":"48","author":"C Yin","year":"2008","journal-title":"Hepatology"},{"issue":"05","key":"ref59","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.cell.2012.03.043","article-title":"Cyclin F-mediated degradation of ribonucleotide reductase M2 controls genome integrity and DNA repair","volume":"149","author":"V D'Angiolella","year":"2012","journal-title":"Cell"},{"issue":"06","key":"ref60","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1002\/hep.26573","article-title":"Hepatocyte nuclear factor-4\u03b1 reverses malignancy of hepatocellular carcinoma through regulating miR-134 in the DLK1-DIO3 region","volume":"58","author":"C Yin","year":"2013","journal-title":"Hepatology"},{"issue":"01","key":"ref61","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1210\/me.2007-0298","article-title":"Nuclear receptor hepatocyte nuclear factor 4alpha1 competes with oncoprotein c-Myc for control of the p21\/WAF1 promoter","volume":"22","author":"W W Hwang-Verslues","year":"2008","journal-title":"Mol Endocrinol"},{"issue":"22","key":"ref62","doi-asserted-by":"crossref","first-page":"8419","DOI":"10.1073\/pnas.0600246103","article-title":"Hepatocyte nuclear factor 4alpha orchestrates expression of cell adhesion proteins during the epithelial transformation of the developing liver","volume":"103","author":"M A Battle","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"04","key":"ref63","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1083\/jcb.140.4.935","article-title":"Hepatocyte nuclear factor 4 provokes expression of epithelial marker genes, acting as a morphogen in dedifferentiated hepatoma cells","volume":"140","author":"G F Sp\u00e4th","year":"1998","journal-title":"J Cell Biol"},{"issue":"40","key":"ref64","doi-asserted-by":"crossref","first-page":"26144","DOI":"10.18632\/oncotarget.25456","article-title":"Loss-of-function mutations in Zn-finger DNA-binding domain of HNF4A cause aberrant transcriptional regulation in liver cancer","volume":"9","author":"H Taniguchi","year":"2018","journal-title":"Oncotarget"},{"issue":"03","key":"ref65","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1093\/carcin\/17.3.609","article-title":"Expression of hepatocyte-enriched nuclear transcription factors in mouse liver tumours","volume":"17","author":"A Kalkuhl","year":"1996","journal-title":"Carcinogenesis"},{"issue":"05","key":"ref66","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1134\/S0026893308050075","article-title":"Hepatocyte nuclear factor 4 (HNF4) in epithelial development and carcinogenesis [in Russian]","volume":"42","author":"N L Lazarevich","year":"2008","journal-title":"Mol Biol (Mosk)"},{"issue":"03","key":"ref67","first-page":"167","article-title":"Deregulation of hepatocyte nuclear factor 4 (HNF4)as a marker of epithelial tumors progression","volume":"32","author":"N L Lazarevich","year":"2010","journal-title":"Exp Oncol"},{"issue":"06","key":"ref68","doi-asserted-by":"crossref","first-page":"9045","DOI":"10.1002\/jcp.27579","article-title":"Identification of TAF1, HNF4A, and CALM2 as potential therapeutic target genes for liver fibrosis","volume":"234","author":"D Ji","year":"2019","journal-title":"J Cell Physiol"},{"issue":"01","key":"ref69","doi-asserted-by":"crossref","first-page":"3126","DOI":"10.1038\/s41467-019-11004-3","article-title":"Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis","volume":"10","author":"J Argemi","year":"2019","journal-title":"Nat Commun"},{"issue":"04","key":"ref70","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1002\/hep.20155","article-title":"Progression of HCC in mice is associated with a downregulation in the expression of hepatocyte nuclear factors","volume":"39","author":"N L Lazarevich","year":"2004","journal-title":"Hepatology"},{"issue":"22","key":"ref71","doi-asserted-by":"crossref","first-page":"5860","DOI":"10.1158\/0008-5472.CAN-19-1277","article-title":"HNF4\u03b1-deficient fatty liver provides a permissive environment for sex-independent hepatocellular carcinoma","volume":"79","author":"B Fekry","year":"2019","journal-title":"Cancer Res"},{"issue":"10","key":"ref72","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1177\/1756283X17725998","article-title":"Increased expression of hepatocyte nuclear factor 4 alpha transcribed by promoter 2 indicates a poor prognosis in hepatocellular carcinoma","volume":"10","author":"S H Cai","year":"2017","journal-title":"Therap Adv Gastroenterol"},{"issue":"05","key":"ref73","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1002\/path.1928","article-title":"Dysregulated expression of P1 and P2 promoter-driven hepatocyte nuclear factor-4alpha in the pathogenesis of human cancer","volume":"208","author":"T Tanaka","year":"2006","journal-title":"J Pathol"},{"issue":"01","key":"ref74","doi-asserted-by":"crossref","first-page":"4349","DOI":"10.1038\/s41467-018-06648-6","article-title":"Incompatibility of the circadian protein BMAL1 and HNF4\u03b1 in hepatocellular carcinoma","volume":"9","author":"B Fekry","year":"2018","journal-title":"Nat Commun"},{"key":"ref75","doi-asserted-by":"crossref","first-page":"1266527","DOI":"10.3389\/fendo.2023.1266527","article-title":"HNF4\u03b1 isoforms regulate the circadian balance between carbohydrate and lipid metabolism in the liver","volume":"14","author":"J R Deans","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"05","key":"ref76","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1038\/s41418-018-0170-z","article-title":"The lncRNA HOTAIR transcription is controlled by HNF4\u03b1-induced chromatin topology modulation","volume":"26","author":"C Battistelli","year":"2019","journal-title":"Cell Death Differ"},{"issue":"08","key":"ref77","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.bbagrm.2015.05.005","article-title":"Epigenetic control of EMT\/MET dynamics: HNF4\u03b1 impacts DNMT3s through miRs-29","volume":"1849","author":"C Cicchini","year":"2015","journal-title":"Biochim Biophys Acta"},{"issue":"25","key":"ref78","doi-asserted-by":"crossref","first-page":"10574","DOI":"10.1074\/jbc.M117.785592","article-title":"An HNF4\u03b1-microRNA-194\/192 signaling axis maintains hepatic cell function","volume":"292","author":"A Morimoto","year":"2017","journal-title":"J Biol Chem"},{"issue":"02","key":"ref79","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1111\/liv.12577","article-title":"Molecular mechanisms controlling the phenotype and the EMT\/MET dynamics of hepatocyte","volume":"35","author":"C Cicchini","year":"2015","journal-title":"Liver 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