A Shortcut from Metabolic-Associated Fatty Liver Disease (MAFLD) to Hepatocellular Carcinoma (HCC): c-MYC a Promising Target for Preventative Strategies and Individualized Therapy

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dc.contributor.authorGuo, Feifei
dc.contributor.authorEstévez Vázquez, Olga
dc.contributor.authorBenede Ubieto, Raquel
dc.contributor.authorMaya Mile, Douglas
dc.contributor.authorZheng, Kang
dc.contributor.authorGallego Durán, Rocío
dc.contributor.authorRojas Ávalos, Ángela
dc.contributor.authorAmpuero, Javier
dc.contributor.authorGómez Del Moral Martín-Consuegra, Manuel María
dc.contributor.authorPhilip, Kaye
dc.contributor.authorEgbuniwe, Isioma U.
dc.contributor.authorChen, Chaobo
dc.contributor.authorSimon, Jorge
dc.contributor.authorDelgado, Teresa C.
dc.contributor.authorMartínez Chantar, Maria L.
dc.contributor.authorSun, Jie
dc.contributor.authorReissing, Johanna
dc.contributor.authorBruns, Tony
dc.contributor.authorLamas Paz, Arantza
dc.contributor.authorWoitok, Marius Maximilian
dc.contributor.authorVaquero Martín, Francisco Javier
dc.contributor.authorRegueiro González-Barros, José Ramón
dc.contributor.authorLiedtke, Christian
dc.contributor.authorTrautwein, Christian
dc.contributor.authorBañares Cañizares, Rafael
dc.contributor.authorCubero Palero, Francisco Javier
dc.contributor.authorNevzorova, Yulia
dc.date.accessioned2023-06-22T10:57:12Z
dc.date.available2023-06-22T10:57:12Z
dc.date.issued2021-12-31
dc.description.abstractBackground: Metabolic-associated fatty liver disease (MAFLD) has risen as one of the leading etiologies for hepatocellular carcinoma (HCC). Oncogenes have been suggested to be responsible for the high risk of MAFLD-related HCC. We analyzed the impact of the proto-oncogene c-MYC in the development of human and murine MAFLD and MAFLD-associated HCC. Methods: alb-myctg mice were studied at baseline conditions and after administration of Western diet (WD) in comparison to WT littermates. c-MYC expression was analyzed in biopsies of patients with MAFLD and MAFLD-associated HCC by immunohistochemistry. Results: Mild obesity, spontaneous hyperlipidaemia, glucose intolerance and insulin resistance were characteristic of 36-week-old alb-myctg mice. Middle-aged alb-myctg exhibited liver steatosis and increased triglyceride content. Liver injury and inflammation were associated with elevated ALT, an upregulation of ER-stress response and increased ROS production, collagen deposition and compensatory proliferation. At 52 weeks, 20% of transgenic mice developed HCC. WD feeding exacerbated metabolic abnormalities, steatohepatitis, fibrogenesis and tumor prevalence. Therapeutic use of metformin partly attenuated the spontaneous MAFLD phenotype of alb-myctg mice. Importantly, upregulation and nuclear localization of c-MYC were characteristic of patients with MAFLD and MAFLD-related HCC. Conclusions: A novel function of c-MYC in MAFLD progression was identified opening new avenues for preventative strategies.en
dc.description.departmentDepto. de Genética, Fisiología y Microbiología
dc.description.facultyFac. de Ciencias Biológicas
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Economía, Comercio y Empresa (España)
dc.description.sponsorshipInstituto de Salud Carlos III
dc.description.sponsorshipFundación La Caixa
dc.description.sponsorshipAsociación Española Contra el Cáncer
dc.description.sponsorshipSociedad Alemana de Investigación
dc.description.sponsorshipFundación Ramón y Cajal
dc.description.sponsorshipUniversidad Complutense de Madrid / Banco Santander
dc.description.sponsorshipGobierno Andaluz / Fondo Europeo de Desarrollo Regional
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/74303
dc.identifier.citationGuo, F., Estévez Vázquez, O., Benede Ubieto, R. et al. «A Shortcut from Metabolic-Associated Fatty Liver Disease (MAFLD) to Hepatocellular Carcinoma (HCC): C-MYC a Promising Target for Preventative Strategies and Individualized Therapy». Cancers, vol. 14, n.o 1, diciembre de 2021, p. 192. DOI.org (Crossref), https://doi.org/10.3390/cancers14010192.
dc.identifier.doi10.3390/cancers14010192
dc.identifier.issn2072-6694
dc.identifier.officialurlhttps://doi.org/10.3390/cancers14010192
dc.identifier.urihttps://hdl.handle.net/20.500.14352/71932
dc.issue.number1
dc.journal.titleCancers
dc.language.isoeng
dc.page.final19
dc.page.initial1
dc.publisherMDPI
dc.relation.projectID(SAF2016-78711), (SAF2017-87919-R); (PID2020-117827RB-IOO), (PID2020-117941RB-IOO), (PID2020-117116RB-I00); (EXOHEP-CM S2017/BMD- 3727); (NanoLiver-CM Y2018/NMT-4949); (AMMF 2018/117); (COST Action CA17112); (UCM-25/2019); (SAR2017-87919R)
dc.relation.projectID(PI16/01842), (PI19/01404); (PI19/00589)
dc.relation.projectID(HR17-00601)
dc.relation.projectID(AECC PROYE20084 REGU)
dc.relation.projectID(SFB1382 Project ID 403224013/A02), (SFB1382 Project ID 403224013/B07).
dc.relation.projectID(RYC-2014-15242), (RYC-2015-17438)
dc.relation.projectID(CT63/19)
dc.relation.projectID(PE-0451-2018)
dc.rightsAtribución 3.0 España
dc.rights.accessRightsopen access
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/es/
dc.subject.cdu616-006.04:616.36
dc.subject.keywordMetabolic-associated fatty liver disease (MAFLD)
dc.subject.keywordc-myc
dc.subject.keywordOncogene
dc.subject.keywordTumorigenesis
dc.subject.keywordMetformin
dc.subject.ucmGastroenterología y hepatología
dc.subject.ucmOncología
dc.subject.unesco3205.03 Gastroenterología
dc.subject.unesco3201.01 Oncología
dc.titleA Shortcut from Metabolic-Associated Fatty Liver Disease (MAFLD) to Hepatocellular Carcinoma (HCC): c-MYC a Promising Target for Preventative Strategies and Individualized Therapyen
dc.typejournal article
dc.volume.number14
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