2026-06-30T03:13:19Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/1074112024-08-08T00:01:43Zcom_20.500.14352_14col_20.500.14352_15

A shortcut from Metabolic-Associated Fatty Liver Disease (MAFLD) to hepatocellular carcinoma (HCC) c-MYC as a promising target for preventative strategies and individualized therapy. Guo, Feifei Estévez Vázquez, Olga Benede Ubieto, Raquel Lamas Paz, Arantza Gómez Del Moral Martín-Consuegra, Manuel María Vaquero Martín, Francisco Javier Regueiro González-Barros, José Ramón Bañares Cañizares, Rafael Cubero Palero, Francisco Javier Nevzorova, Yulia Background: 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. 2024-08-07T07:20:10Z 2024-08-07T07:20:10Z 2021-12-31 journal article Guo, F.; Estévez-Vázquez, O.; Benedé-Ubieto, R.; Maya-Miles, D.; Zheng, K.; Gallego-Durán, R.; Rojas, Á.; Ampuero, J.; Romero-Gómez, M.; Philip, K.; 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 2022, 14, 192. https://doi.org/10.3390/ cancers14010192 10.3390/cancers14010192 https://hdl.handle.net/20.500.14352/107411 2072-6694 https://doi.org/10.3390/cancers14010192 https://www.mdpi.com/2072-6694/14/1/192 eng 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 HR17-00601 AECC PROYE20084REGU 403224013/A02 http://creativecommons.org/licenses/by/4.0/ open access Attribution 4.0 International MDPI