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

Guo, FeifeiEstevez-Vazquez, OlgaBenede-Ubieto, RaquelMaya-Miles, DouglasZheng, KangGallego-Duran, RocioRojas, AngelaAmpuero, JavierRomero-Gomez, ManuelPhilip, KayeEgbuniwe, Isioma UChen, ChaoboSimon, JorgeDelgado, Teresa CMartinez-Chantar, Maria LuzSun, JieReissing, JohannaBruns, TonyLamas-Paz, ArantzaGomez-del-Moral, ManuelWoitok, Marius MaximilianVaquero, JavierRegueiro, Jose RLiedtke, ChristianTrautwein, ChristianBañares, RafaelCubero, Francisco JavierNevzorova, Yulia A2023-05-032023-05-032021-12-31Guo F, Estévez-Vázquez O, Benedé-Ubieto R, Maya-Miles D, Zheng K, Gallego-Durán 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 (Basel). 2021 Dec 31;14(1):192.2072-6694http://hdl.handle.net/10668/20863Metabolic-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. 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. 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. A novel function of c-MYC in MAFLD progression was identified opening new avenues for preventative strategies.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/c-mycmetabolic-associated fatty liver disease (MAFLD)metforminoncogenetumorigenesisCarcinoma, HepatocellularReactive Oxygen SpeciesMetforminHyperlipidemiasImmunohistochemistryLiver NeoplasmsBiopsyTriglyceridesDiet, WesternA Shortcut from Metabolic-Associated Fatty Liver Disease (MAFLD) to Hepatocellular Carcinoma (HCC): c-MYC a Promising Target for Preventative Strategies and Individualized Therapy.research article35008356open accessHígado grasoEnfermedadTriglicéridosEconomíaFenotipoInflamaciónOncogenesColágenoIntolerancia a la glucosaResistencia a la insulina10.3390/cancers14010192PMC8750626https://www.mdpi.com/2072-6694/14/1/192/pdf?version=1641447199https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8750626/pdf