Guo, FeifeiEstévez Vázquez, OlgaBenede Ubieto, RaquelMaya Mile, DouglasZheng, KangGallego Durán, RocíoRojas Ávalos, ÁngelaAmpuero, JavierGómez Del Moral Martín-Consuegra, Manuel MaríaPhilip, KayeEgbuniwe, Isioma U.Chen, ChaoboSimon, JorgeDelgado, Teresa C.Martínez Chantar, Maria L.Sun, JieReissing, JohannaBruns, TonyLamas Paz, ArantzaWoitok, Marius MaximilianVaquero Martín, Francisco JavierRegueiro González-Barros, José RamónLiedtke, ChristianTrautwein, ChristianBañares Cañizares, RafaelCubero Palero, Francisco JavierNevzorova, Yulia2023-06-222023-06-222021-12-31Guo, 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/cancers14010192.2072-669410.3390/cancers14010192https://hdl.handle.net/20.500.14352/71932Background: 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.engAtribución 3.0 Españahttps://creativecommons.org/licenses/by/3.0/es/journal articlehttps://doi.org/10.3390/cancers14010192open access616-006.04:616.36Metabolic-associated fatty liver disease (MAFLD)c-mycOncogeneTumorigenesisMetforminGastroenterología y hepatologíaOncología3205.03 Gastroenterología3201.01 Oncología