RT Journal Article
T1 A Shortcut from Metabolic-Associated Fatty Liver Disease (MAFLD) to Hepatocellular Carcinoma (HCC): c-MYC a Promising Target for Preventative Strategies and Individualized Therapy
A1 Guo, Feifei
A1 Estevez Vázquez, Olga
A1 Benedé Ubieto, Raquel
A1 Maya Mile, Douglas
A1 Zheng, Kang
A1 Gallego Durán, Rocío
A1 Rojas Ávalos, Ángela
A1 Ampuero, Javier
A1 Romero Gómez, Manuel
A1 Philip, Kaye
A1 Egbuniwe, Isioma U.
A1 Chen, Chaobo
A1 Simon, Jorge
A1 Delgado, Teresa C.
A1 Martínez Chantar, Maria L.
A1 Sun, Jie
A1 Reissing, Johanna
A1 Bruns, Tony
A1 Lamas Paz, Arantza
A1 Woitok, Marius Maximilian
A1 Regueiro, José R.
A1 Liedtke, Christian
A1 Trautwein, Christian
A1 Bañares Cañizares, Rafael
A1 Cubero Palero, Francisco Javier
A1 Benede Ubieto, Raquel
A1 Gómez Del Moral Martín-Consuegra, Manuel María
A1 Vaquero Martín, Francisco Javier
A1 Nevzorova, Yulia
AB 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.
PB MDPI
SN 2072-6694
YR 2021
FD 2021-12-31
LK https://hdl.handle.net/20.500.14352/71932
UL https://hdl.handle.net/20.500.14352/71932
LA eng
NO Ministerio de Economía y Competitividad (MINECO)
NO Instituto de Salud Carlos III (ISCIII)
NO Fundación La Caixa
NO Asociación Española Contra el Cáncer  (AECC)
NO German Research Foundation
NO Fundación Ramón y Cajal
NO Universidad Complutense de Madrid / Banco Santander
NO Gobierno Andaluz / FEDER
DS Docta Complutense
RD 21 ago 2024