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

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...

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Detalles Bibliográficos
Autores: Guo, Feifei, Estévez Vázquez, Olga, Benede Ubieto, Raquel, Maya Mile, Douglas, Zheng, Kang, Gallego Durán, Rocío, Rojas Ávalos, Ángela, Ampuero, Javier, Gómez Del Moral Martín-Consuegra, Manuel María, Philip, Kaye, Egbuniwe, Isioma U., Chen, Chaobo, Simon, Jorge, Delgado, Teresa C., Martínez Chantar, Maria L., Sun, Jie, Reissing, Johanna, Bruns, Tony, Lamas Paz, Arantza, Woitok, Marius Maximilian, Vaquero Martín, Francisco Javier, Regueiro González-Barros, José Ramón, Liedtke, Christian, Trautwein, Christian, Bañares Cañizares, Rafael, Cubero Palero, Francisco Javier, Nevzorova, Yulia
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/71932
Acceso en línea:https://hdl.handle.net/20.500.14352/71932
Access Level:acceso abierto
Palabra clave:616-006.04:616.36
Metabolic-associated fatty liver disease (MAFLD)
c-myc
Oncogene
Tumorigenesis
Metformin
Gastroenterología y hepatología
Oncología
3205.03 Gastroenterología
3201.01 Oncología
Descripción
Sumario: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.

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