Controversial roles of hepatocyte nuclear receptor 4 α on tumorigenesis (Review)
- Authors:
- Zhu Wang
- Ying Zhang
- Jianwen Zhang
- Qiong Deng
- Hui Liang
-
Affiliations: Department of Urology, People's Hospital of Longhua, Southern Medical University, Shenzhen, Guangdong 518109, P.R. China - Published online on: March 4, 2021 https://doi.org/10.3892/ol.2021.12617
- Article Number: 356
-
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
 |
 |
 |
 |
|
Kiselyuk A, Lee SH, Farber-Katz S, Zhang M, Athavankar S, Cohen T, Pinkerton AB, Ye M, Bushway P, Richardson AD, et al: HNF4α antagonists discovered by a high-throughput screen for modulators of the human insulin promoter. Chem Biol. 19:806–818. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Duncan SA, Manova K, Chen WS, Hoodless P, Weinstein DC, Bachvarova RF and Darnell JE Jr: Expression of transcription factor HNF-4 in the extraembryonic endoderm, gut, and nephrogenic tissue of the developing mouse embryo: HNF-4 is a marker for primary endoderm in the implanting blastocyst. Proc Natl Acad Sci USA. 91:7598–7602. 1994. View Article : Google Scholar : PubMed/NCBI | |
|
Huang J, Karakucuk V, Levitsky LL and Rhoads DB: Expression of HNF4alpha variants in pancreatic islets and Ins-1 beta cells. Diabetes Metab Res Rev. 24:533–543. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Harries LW, Locke JM, Shields B, Hanley NA, Hanley KP, Steele A, Njølstad PR, Ellard S and Hattersley AT: The diabetic phenotype in HNF4A mutation carriers is moderated by the expression of HNF4A isoforms from the P1 promoter during fetal development. Diabetes. 57:1745–1752. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Hwang-Verslues WW and Sladek FM: HNF4alpha-role in drug metabolism and potential drug target? Curr Opin Pharmacol. 10:698–705. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Hertz R, Magenheim J, Berman I and Bar-Tana J: Fatty acyl-CoA thioesters are ligands of hepatic nuclear factor-4alpha. Nature. 392:512–516. 1998. View Article : Google Scholar : PubMed/NCBI | |
|
Bogan AA, Dallas-Yang Q, Ruse MD Jr, Maeda Y, Jiang G, Nepomuceno L, Scanlan TS, Cohen FE and Sladek FM: Analysis of protein dimerization and ligand binding of orphan receptor HNF4alpha. J Mol Biol. 302:831–851. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Dhe-Paganon S, Duda K, Iwamoto M, Chi YI and Shoelson SE: Crystal structure of the HNF4 alpha ligand binding domain in complex with endogenous fatty acid ligand. J Biol Chem. 277:37973–37976. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Wisely GB, Miller AB, Davis RG, Thornquest AD Jr, Johnson R, Spitzer T, Sefler A, Shearer B, Moore JT, Miller AB, et al: Hepatocyte nuclear factor 4 is a transcription factor that constitutively binds fatty acids. Structure. 10:1225–1234. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Benoit G, Malewicz M and Perlmann T: Digging deep into the pockets of orphan nuclear receptors: Insights from structural studies. Trends Cell Biol. 14:369–376. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Sladek F: Desperately seeking…something. Mol Cell. 10:219–221. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Yuan X, Ta TC, Lin M, Evans JR, Dong Y, Bolotin E, Sherman MA, Forman BM and Sladek FM: Identification of an endogenous ligand bound to a native orphan nuclear receptor. PLoS One. 4:e56092009. View Article : Google Scholar : PubMed/NCBI | |
|
Lee SH, Piran R, Keinan E, Pinkerton A and Levine F: Induction of beta-cell replication by a synthetic HNF4alpha antagonist. Stem Cells. 31:2396–2407. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Kiselyuk A, Farber-Katz S, Cohen T, Lee SH, Geron I, Azimi B, Heynen-Genel S, Singer O, Price J, Mercola M, et al: Phenothiazine neuroleptics signal to the human insulin promoter as revealed by a novel high-throughput screen. J Biomol Screen. 15:663–670. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Fujimura T, Sakuma H, Konishi S, Oe T, Hosogai N, Kimura C, Aramori I and Mutoh S: FK614, a novel peroxisome proliferator-activated receptor gamma modulator, induces differential transactivation through a unique ligand-specific interaction with transcriptional coactivators. J Pharmacol Sci. 99:342–352. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Inoue Y, Yu AM, Yim SH, Ma X, Krausz KW, Inoue J, Xiang CC, Brownstein MJ, Eggertsen G, Björkhem I and Gonzalez FJ: Regulation of bile acid biosynthesis by hepatocyte nuclear factor 4alpha. J Lipid Res. 47:215–227. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Chiang JY: Hepatocyte nuclear factor 4alpha regulation of bile acid and drug metabolism. Expert Opin Drug Metab Toxicol. 5:137–147. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Nitta S, Kusakari Y, Yamada Y, Kubo T, Neo S, Igarashi H and Hisasue M: Conversion of mesenchymal stem cells into a canine hepatocyte-like cells by Foxa1 and Hnf4a. Regen Ther. 14:165–176. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Chen S, Lencinas A, Nunez M, Selmin OI and Runyan RB: HNF4a transcription is a target of trichloroethylene toxicity in the embryonic mouse heart. Environ Sci Process Impacts. 22:824–832. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Jover R, Moya M and Gomez-Lechon MJ: Transcriptional regulation of cytochrome p450 genes by the nuclear receptor hepatocyte nuclear factor 4-alpha. Curr Drug Metab. 10:508–519. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Tavares-Sanchez OL, Rodriguez C, Gortares-Moroyoqui P and Estrada MI: Hepatocyte nuclear factor-4alpha, a multifunctional nuclear receptor associated with cardiovascular disease and cholesterol catabolism. Int J Environ Health Res. 25:126–139. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Kyrmizi I, Hatzis P, Katrakili N, Tronche F, Gonzalez FJ and Talianidis I: Plasticity and expanding complexity of the hepatic transcription factor network during liver development. Genes Dev. 20:2293–2305. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Li J, Ning G and Duncan SA: Mammalian hepatocyte differentiation requires the transcription factor HNF-4alpha. Genes Dev. 14:464–474. 2000.PubMed/NCBI | |
|
Hayhurst GP, Lee YH, Lambert G, Ward JM and Gonzalez FJ: Hepatocyte nuclear factor 4alpha (nuclear receptor 2A1) is essential for maintenance of hepatic gene expression and lipid homeostasis. Mol Cell Biol. 21:1393–1403. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Parviz F, Matullo C, Garrison WD, Savatski L, Adamson JW, Ning G, Kaestner KH, Rossi JM, Zaret KS and Duncan SA: Hepatocyte nuclear factor 4alpha controls the development of a hepatic epithelium and liver morphogenesis. Nat Genet. 34:292–296. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Lussier CR, Babeu JP, Auclair BA, Perreault N and Boudreau F: Hepatocyte nuclear factor-4alpha promotes differentiation of intestinal epithelial cells in a coculture system. Am J Physiol Gastrointest Liver Physiol. 294:G418–G428. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Garrison WD, Battle MA, Yang C, Kaestner KH, Sladek FM and Duncan SA: Hepatocyte nuclear factor 4alpha is essential for embryonic development of the mouse colon. Gastroenterology. 130:1207–1220. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
DeLaForest A, Nagaoka M, Si-Tayeb K, Noto FK, Konopka G, Battle MA and Duncan SA: HNF4A is essential for specification of hepatic progenitors from human pluripotent stem cells. Development. 138:4143–4153. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Grigo K, Wirsing A, Lucas B, Klein-Hitpass L and Ryffel GU: HNF4 alpha orchestrates a set of 14 genes to down-regulate cell proliferation in kidney cells. Biol Chem. 389:179–187. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Erdmann S, Senkel S, Arndt T, Lucas B, Lausen J, Klein-Hitpass L, Ryffel GU and Thomas H: Tissue-specific transcription factor HNF4alpha inhibits cell proliferation and induces apoptosis in the pancreatic INS-1 beta-cell line. Biol Chem. 388:91–106. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Santangelo L, Marchetti A, Cicchini C, Conigliaro A, Conti B, Mancone C, Bonzo JA, Gonzalez FJ, Alonzi T, Amicone L and Tripodi M: The stable repression of mesenchymal program is required for hepatocyte identity: A novel role for hepatocyte nuclear factor 4α. Hepatology. 53:2063–2074. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Thiery JP and Sleeman JP: Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol. 7:131–142. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Thiery JP, Acloque H, Huang RY and Nieto MA: Epithelial-mesenchymal transitions in development and disease. Cell. 139:871–890. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Ahn SH, Shah YM, Inoue J, Morimura K, Kim I, Yim S, Lambert G, Kurotani R, Nagashima K, Gonzalez FJ and Inoue Y: Hepatocyte nuclear factor 4alpha in the intestinal epithelial cells protects against inflammatory bowel disease. Inflamm Bowel Dis. 14:908–920. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Darsigny M, Babeu JP, Dupuis AA, Furth EE, Seidman EG, Lévy E, Verdu EF, Gendron FP and Boudreau F: Loss of hepatocyte-nuclear-factor-4alpha affects colonic ion transport and causes chronic inflammation resembling inflammatory bowel disease in mice. PLoS One. 4:e76092009. View Article : Google Scholar : PubMed/NCBI | |
|
Tanaka T, Jiang S, Hotta H, Takano K, Iwanari H, Sumi K, Daigo K, Ohashi R, Sugai M, Ikegame C, et al: Dysregulated expression of P1 and P2 promoter-driven hepatocyte nuclear factor-4alpha in the pathogenesis of human cancer. J Pathol. 208:662–672. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Oshima T, Kawasaki T, Ohashi R, Hasegawa G, Jiang S, Umezu H, Aoyagi Y, Iwanari H, Tanaka T, Hamakubo T, et al: Downregulated P1 promoter-driven hepatocyte nuclear factor-4alpha expression in human colorectal carcinoma is a new prognostic factor against liver metastasis. Pathol Int. 57:82–90. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Takano K, Hasegawa G, Jiang S, Kurosaki I, Hatakeyama K, Iwanari H, Tanaka T, Hamakubo T, Kodama T and Naito M: Immunohistochemical staining for P1 and P2 promoter-driven hepatocyte nuclear factor-4alpha may complement mucin phenotype of differentiated-type early gastric carcinoma. Pathol Int. 59:462–470. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Lambert E, Babeu JP, Simoneau J, Raisch J, Lavergne L, Lévesque D, Jolibois É, Avino M, Scott MS, Boudreau F and Boisvert FM: Human hepatocyte nuclear factor 4-alpha encodes isoforms with distinct transcriptional functions. Mol Cell Proteomics. 19:808–827. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Vuong LM, Chellappa K, Dhahbi JM, Deans JR, Fang B, Bolotin E, Titova NV, Hoverter NP, Spindler SR, Waterman ML and Sladek FM: Differential effects of hepatocyte nuclear factor 4alpha isoforms on tumor growth and T-cell factor 4/AP-1 interactions in human colorectal cancer cells. Mol Cell Biol. 35:3471–3490. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Babeu JP, Jones C, Geha S, Carrier JC and Boudreau F: P1 promoter-driven HNF4alpha isoforms are specifically repressed by beta-catenin signaling in colorectal cancer cells. J Cell Sci. 131:jcs2147342018. View Article : Google Scholar : PubMed/NCBI | |
|
Hoadley KA, Yau C, Hinoue T, Wolf DM, Lazar AJ, Drill E, Shen R, Taylor AM, Cherniack AD, Thorsson V, et al: Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer. Cell. 173:291–304.e6. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Zhou B and Guo R: Genomic and regulatory characteristics of significant transcription factors in colorectal cancer metastasis. Sci Rep. 8:178362018. View Article : Google Scholar : PubMed/NCBI | |
|
Chellappa K, Deol P, Evans JR, Vuong LM, Chen G, Briançon N, Bolotin E, Lytle C, Nair MG and Sladek FM: Opposing roles of nuclear receptor HNF4α isoforms in colitis and colitis-associated colon cancer. Elife. 5:e109032016. View Article : Google Scholar : PubMed/NCBI | |
|
Yao HS, Wang J, Zhang XP, Wang LZ, Wang Y, Li XX, Jin KZ, Hu ZQ and Wang WJ: Hepatocyte nuclear factor 4α suppresses the aggravation of colon carcinoma. Mol Carcinog. 55:458–472. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Babeu JP, Wilson SD, Lambert E, Levesque D, Boisvert FM and Boudreau F: Quantitative proteomics identifies DNA repair as a novel biological function for hepatocyte nuclear factor 4α in colorectal cancer cells. Cancers (Basel). 11:6262019. View Article : Google Scholar | |
|
Yokoyama A, Katsura S, Ito R, Hashiba W, Sekine H, Fujiki R and Kato S: Multiple post-translational modifications in hepatocyte nuclear factor 4alpha. Biochem Biophys Res Commun. 410:749–753. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Zhou W, Hannoun Z, Jaffray E, Medine CN, Black JR, Greenhough S, Zhu L, Ross JA, Forbes S, Wilmut I, et al: SUMOylation of HNF4α regulates protein stability and hepatocyte function. J Cell Sci. 125:3630–3635. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Daigo K, Kawamura T, Ohta Y, Ohashi R, Katayose S, Tanaka T, Aburatani H, Naito M, Kodama T, Ihara S and Hamakubo T: Proteomic analysis of native hepatocyte nuclear factor-4α (HNF4α) isoforms, phosphorylation status, and interactive cofactors. J Biol Chem. 286:674–686. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Lazarevich NL, Cheremnova OA, Varga EV, Ovchinnikov DA, Kudrjavtseva EI, Morozova OV, Fleishman DI, Engelhardt NV and Duncan SA: Progression of HCC in mice is associated with a downregulation in the expression of hepatocyte nuclear factors. Hepatology. 39:1038–1047. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Xu L, Hui L, Wang S, Gong J, Jin Y, Wang Y, Ji Y, Wu X, Han Z and Hu G: Expression profiling suggested a regulatory role of liver-enriched transcription factors in human hepatocellular carcinoma. Cancer Res. 61:3176–3181. 2001.PubMed/NCBI | |
|
Wu N, Zhang YL, Wang HT, Li DW, Dai HJ, Zhang QQ, Zhang J, Ma Y, Xia Q, Bian JM and Hang HL: Overexpression of hepatocyte nuclear factor 4α in human mesenchymal stem cells suppresses hepatocellular carcinoma development through Wnt/β-catenin signaling pathway downregulation. Cancer Biol Ther. 17:558–565. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Ning BF, Ding J, Yin C, Zhong W, Wu K, Zeng X, Yang W, Chen YX, Zhang JP, Zhang X, et al: Hepatocyte nuclear factor 4 alpha suppresses the development of hepatocellular carcinoma. Cancer Res. 70:7640–7651. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Saandi T, Baraille F, Derbal-Wolfrom L, Cattin AL, Benahmed F, Martin E, Cardot P, Duclos B, Ribeiro A, Freund JN and Duluc I: Regulation of the tumor suppressor homeogene Cdx2 by HNF4α in intestinal cancer. Oncogene. 32:3782–3788. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Chiba H, Itoh T, Satohisa S, Sakai N, Noguchi H, Osanai M, Kojima T and Sawada N: Activation of p21CIP1/WAF1 gene expression and inhibition of cell proliferation by overexpression of hepatocyte nuclear factor-4alpha. Exp Cell Res. 302:11–21. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Z, Li Y, Wu D, Yu S, Wang Y and Leung Chan F: Nuclear receptor HNF4alpha performs a tumor suppressor function in prostate cancer via its induction of p21-driven cellular senescence. Oncogene. 39:1572–1589. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Hwang-Verslues WW and Sladek FM: Nuclear receptor hepatocyte nuclear factor 4alpha1 competes with oncoprotein c-Myc for control of the p21/WAF1 promoter. Mol Endocrinol. 22:78–90. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Lu JW, Hsia Y, Yang WY, Lin YI, Li CC, Tsai TF, Chang KW, Shieh GS, Tsai SF, Wang HD and Yuh CH: Identification of the common regulators for hepatocellular carcinoma induced by hepatitis B virus X antigen in a mouse model. Carcinogenesis. 33:209–219. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Walesky C, Edwards G, Borude P, Gunewardena S, O'Neil M, Yoo B and Apte U: Hepatocyte nuclear factor 4 alpha deletion promotes diethylnitrosamine-induced hepatocellular carcinoma in rodents. Hepatology. 57:2480–2490. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Walesky C and Apte U: Role of hepatocyte nuclear factor 4α (HNF4α) in cell proliferation and cancer. Gene Expr. 16:101–108. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Hanse EA, Mashek DG, Becker JR, Solmonson AD, Mullany LK, Mashek MT, Towle HC, Chau AT and Albrecht JH: Cyclin D1 inhibits hepatic lipogenesis via repression of carbohydrate response element binding protein and hepatocyte nuclear factor 4α. Cell Cycle. 11:2681–2690. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Gao Y, Yan Y, Guo J, Zhang Q, Bi D, Wang F, Chang Z, Lu L, Yao X and Wei Q: HNF4α downregulation promotes tumor migration and invasion by regulating Ecadherin in renal cell carcinoma. Oncol Rep. 42:1066–1074. 2019.PubMed/NCBI | |
|
Zhou H, Guo L, Yao W, Shi R, Yu G, Xu H and Ye Z: Silencing of tumor-suppressive NR_023387 in renal cell carcinoma via promoter hypermethylation and HNF4A deficiency. J Cell Physiol. 235:2113–2128. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Lu J, Chen Z, Zhao H, Dong H, Zhu L, Zhang Y, Wang J, Zhu H, Cui Q, Qi C, et al: ABAT and ALDH6A1, regulated by transcription factor HNF4A, suppress tumorigenic capability in clear cell renal cell carcinoma. J Transl Med. 18:1012020. View Article : Google Scholar : PubMed/NCBI | |
|
Saha SK, Parachoniak CA, Ghanta KS, Fitamant J, Ross KN, Najem MS, Gurumurthy S, Akbay EA, Sia D, Cornella H, et al: Mutant IDH inhibits HNF-4α to block hepatocyte differentiation and promote biliary cancer. Nature. 513:110–114. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Yang G, Zhang M, Zhao Y, Pan Y, Kan M, Li J, He K and Zhang X: HNF-4α inhibits hepatocellular carcinoma cell proliferation through mir-122-adam17 pathway. PLoS One. 15:e02304502020. View Article : Google Scholar : PubMed/NCBI | |
|
Lv DD, Zhou LY and Tang H: Hepatocyte nuclear factor 4α and cancer-related cell signaling pathways: A promising insight into cancer treatment. Exp Mol Med. 53:8–18. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Z and Burke PA: The role of microRNAs in hepatocyte nuclear factor-4alpha expression and transactivation. Biochim Biophys Acta. 1829:436–442. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Deng XG, Qiu RL, Wu YH, Li ZX, Xie P, Zhang J, Zhou JJ, Zeng LX, Tang J, Maharjan A and Deng JM: Overexpression of miR-122 promotes the hepatic differentiation and maturation of mouse ESCs through a miR-122/FoxA1/HNF4a-positive feedback loop. Liver Int. 34:281–295. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Ning BF, Ding J, Liu J, Yin C, Xu WP, Cong WM, Zhang Q, Chen F, Han T, Deng X, et al: Hepatocyte nuclear factor 4α-nuclear factor-κB feedback circuit modulates liver cancer progression. Hepatology. 60:1607–1619. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Takagi S, Nakajima M, Kida K, Yamaura Y, Fukami T and Yokoi T: MicroRNAs regulate human hepatocyte nuclear factor 4alpha, modulating the expression of metabolic enzymes and cell cycle. J Biol Chem. 285:4415–4422. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Salloum-Asfar S, Arroyo AB, Teruel-Montoya R, García-Barberá N, Roldán V, Vicente V, Martínez C and González-Conejero R: MiRNA-based regulation of hemostatic factors through hepatic nuclear Factor-4 alpha. PLoS One. 11:e01547512016. View Article : Google Scholar : PubMed/NCBI | |
|
Ramamoorthy A, Li L, Gaedigk A, Bradford LD, Benson EA, Flockhart DA and Skaar TC: In silico and in vitro identification of microRNAs that regulate hepatic nuclear factor 4α expression. Drug Metab Dispos. 40:726–733. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Koh W, Sheng CT, Tan B, Lee QY, Kuznetsov V, Kiang LS and Tanavde V: Analysis of deep sequencing microRNA expression profile from human embryonic stem cells derived mesenchymal stem cells reveals possible role of let-7 microRNA family in downstream targeting of hepatic nuclear factor 4 alpha. BMC Genomics. 11 (Suppl 1):S62010. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang X, Xu Y, Qian Z, Zheng W, Wu Q, Chen Y, Zhu G, Liu Y, Bian Z, Xu W, et al: circRNA_104075 stimulates YAP-dependent tumorigenesis through the regulation of HNF4a and may serve as a diagnostic marker in hepatocellular carcinoma. Cell Death Dis. 9:10912018. View Article : Google Scholar : PubMed/NCBI | |
|
Moon RT and Miller JR: The APC tumor suppressor protein in development and cancer. Trends Genet. 13:256–258. 1997. View Article : Google Scholar : PubMed/NCBI | |
|
Yang M, Li SN, Anjum KM, Gui LX, Zhu SS, Liu J, Chen JK, Liu QF, Ye GD, Wang WJ, et al: A double-negative feedback loop between Wnt-β-catenin signaling and HNF4α regulates epithelial-mesenchymal transition in hepatocellular carcinoma. J Cell Sci. 126:5692–5703. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Battle MA, Konopka G, Parviz F, Gaggl AL, Yang C, Sladek FM and Duncan SA: Hepatocyte nuclear factor 4alpha orchestrates expression of cell adhesion proteins during the epithelial transformation of the developing liver. Proc Natl Acad Sci USA. 103:8419–8424. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Lazarevich NL, Shavochkina DA, Fleishman DI, Kustova IF, Morozova OV, Chuchuev ES and Patyutko YI: Deregulation of hepatocyte nuclear factor 4 (HNF4) as a marker of epithelial tumors progression. Exp Oncol. 32:167–171. 2010.PubMed/NCBI | |
|
Yao D, Peng S and Dai C: The role of hepatocyte nuclear factor 4alpha in metastatic tumor formation of hepatocellular carcinoma and its close relationship with the mesenchymal-epithelial transition markers. BMC Cancer. 13:4322013. View Article : Google Scholar : PubMed/NCBI | |
|
Huang Q, Pu M, Zhao G, Dai B, Bian Z, Tang H, Chen C, Liu W, Qu X, Shen L and Tao K: Tg737 regulates epithelial-mesenchymal transition and cancer stem cell properties via a negative feedback circuit between Snail and HNF4α during liver stem cell malignant transformation. Cancer Lett. 402:52–60. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Yin C, Lin Y, Zhang X, Chen YX, Zeng X, Yue HY, Hou JL, Deng X, Zhang JP, Han ZG and Xie WF: Differentiation therapy of hepatocellular carcinoma in mice with recombinant adenovirus carrying hepatocyte nuclear factor-4alpha gene. Hepatology. 48:1528–1539. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Stumpf H, Senkel S, Rabes HM and Ryffel GU: The DNA binding activity of the liver transcription factors LFB1 (HNF1) and HNF4 varies coordinately in rat hepatocellular carcinoma. Carcinogenesis. 16:143–145. 1995. View Article : Google Scholar : PubMed/NCBI | |
|
Flodby P, Liao DZ, Blanck A, Xanthopoulos KG and Hallstrom IP: Expression of the liver-enriched transcription factors C/EBP alpha, C/EBP beta, HNF-1, and HNF-4 in preneoplastic nodules and hepatocellular carcinoma in rat liver. Mol Carcinog. 12:103–109. 1995. View Article : Google Scholar : PubMed/NCBI | |
|
Choi JK, Choi JY, Kim DG, Choi DW, Kim BY, Lee KH, Yeom YI, Yoo HS, Yoo OJ and Kim S: Integrative analysis of multiple gene expression profiles applied to liver cancer study. FEBS Lett. 565:93–100. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Cai SH, Lu SX, Liu LL, Zhang CZ and Yun JP: Increased expression of hepatocyte nuclear factor 4 alpha transcribed by promoter 2 indicates a poor prognosis in hepatocellular carcinoma. Therap Adv Gastroenterol. 10:761–771. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang X, Du L, Qiao Y, Zhang X, Zheng W, Wu Q, Chen Y, Zhu G, Liu Y, Bian Z, et al: Ferroptosis is governed by differential regulation of transcription in liver cancer. Redox Biol. 24:1012112019. View Article : Google Scholar : PubMed/NCBI | |
|
Darsigny M, Babeu JP, Seidman EG, Gendron FP, Levy E, Carrier J, Perreault N and Boudreau F: Hepatocyte nuclear Factor-4alpha promotes gut neoplasia in mice and protects against the production of reactive oxygen species. Cancer Res. 70:9423–9433. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Kriegsmann M, Harms A, Longuespée R, Muley T, Winter H, Kriegsmann K, Kazdal D, Goeppert B, Pathil A and Warth A: Role of conventional immunomarkers, HNF4-α and SATB2, in the differential diagnosis of pulmonary and colorectal adenocarcinomas. Histopathology. 72:997–1006. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Sugai M, Umezu H, Yamamoto T, Jiang S, Iwanari H, Tanaka T, Hamakubo T, Kodama T and Naito M: Expression of hepatocyte nuclear factor 4 alpha in primary ovarian mucinous tumors. Pathol Int. 58:681–686. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Xiang X, Zhao X, Qu H, Li D, Yang D, Pu J, Mei H, Zhao J, Huang K, Zheng L and Tong Q: Hepatocyte nuclear factor 4 alpha promotes the invasion, metastasis and angiogenesis of neuroblastoma cells via targeting matrix metalloproteinase 14. Cancer Lett. 359:187–197. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Sugano M, Nagasaka T, Sasaki E, Murakami Y, Hosoda W, Hida T, Mitsudomi T and Yatabe Y: HNF4α as a marker for invasive mucinous adenocarcinoma of the lung. Am J Surg Pathol. 37:211–218. 2012. View Article : Google Scholar | |
|
Li Z and Chen H: miR-34a inhibits proliferation, migration and invasion of paediatric neuroblastoma cells via targeting HNF4α. Artif Cells Nanomed Biotechnol. 47:3072–3078. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Sun Q, Xu W, Ji S, Qin Y, Liu W, Hu Q, Zhang Z, Liu M, Yu X and Xu X: Role of hepatocyte nuclear factor 4 alpha in cell proliferation and gemcitabine resistance in pancreatic adenocarcinoma. Cancer Cell Int. 19:492019. View Article : Google Scholar : PubMed/NCBI | |
|
Xu C, Ooi WF, Qamra A, Tan J, Chua BY, Ho SWT, Das K, Adam Isa ZF, Li Z, Yao X, et al: HNF4α pathway mapping identifies wild-type IDH1 as a targetable metabolic node in gastric cancer. Gut. 69:231–242. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Chang HR, Nam S, Kook MC, Kim KT, Liu X, Yao H, Jung HR, Lemos R Jr, Seo HH, Park HS, et al: HNF4α is a therapeutic target that links AMPK to WNT signalling in early-stage gastric cancer. Gut. 65:19–32. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Ma Y, Wei X and Wu Z: HNF-4α promotes multidrug resistance of gastric cancer cells through the modulation of cell apoptosis. Oncol Lett. 14:6477–6484. 2017.PubMed/NCBI | |
|
Nakajima N, Yoshizawa A, Nakajima T, Hirata M, Furuhata A, Sumiyoshi S, Rokutan-Kurata M, Sonobe M, Menju T, Miyamoto E, et al: GATA6-positive lung adenocarcinomas are associated with invasive mucinous adenocarcinoma morphology, hepatocyte nuclear factor 4α expression, and KRAS mutations. Histopathology. 73:38–48. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Chia NY, Deng N, Das K, Huang D, Hu L, Zhu Y, Lim KH, Lee MH, Wu J, Sam XX, et al: Regulatory crosstalk between lineage-survival oncogenes KLF5, GATA4 and GATA6 cooperatively promotes gastric cancer development. Gut. 64:707–719. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Z, Wu D, Ng CF, Teoh JY, Yu S, Wang Y and Chan FL: Nuclear receptor profiling in prostatospheroids and castration-resistant prostate cancer. Endocr Relat Cancer. 25:35–50. 2018. View Article : Google Scholar : PubMed/NCBI |
