%0 Journal Article
%A Guo, Feifei
%A Estevez-Vazquez, Olga
%A Benede-Ubieto, Raquel
%A Maya-Miles, Douglas
%A Zheng, Kang
%A Gallego-Duran, Rocio
%A Rojas, Angela
%A Ampuero, Javier
%A Romero-Gomez, Manuel
%A Philip, Kaye
%A Egbuniwe, Isioma U
%A Chen, Chaobo
%A Simon, Jorge
%A Delgado, Teresa C
%A Martinez-Chantar, Maria Luz
%A Sun, Jie
%A Reissing, Johanna
%A Bruns, Tony
%A Lamas-Paz, Arantza
%A Gomez-del-Moral, Manuel 
%A Woitok, Marius Maximilian
%A Vaquero, Javier
%A Regueiro, Jose R
%A Liedtke, Christian
%A Trautwein, Christian
%A Bañares, Rafael
%A Cubero, Francisco Javier
%A Nevzorova, Yulia A
%T A Shortcut from Metabolic-Associated Fatty Liver Disease (MAFLD) to Hepatocellular Carcinoma (HCC): c-MYC a Promising Target for Preventative Strategies and Individualized Therapy.
%D 2021
%@ 2072-6694
%U http://hdl.handle.net/10668/20863
%X 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. 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.
%K c-myc
%K metabolic-associated fatty liver disease (MAFLD)
%K metformin
%K oncogene
%K tumorigenesis
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