Person:
Gómez Del Moral Martín-Consuegra, Manuel María

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First Name
Manuel María
Last Name
Gómez Del Moral Martín-Consuegra
URI
https://hdl.handle.net/20.500.14352/79627
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Biología Celular
Area
Biología Celular
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Item Type: Publication × Subject: 616-006.04:616.36 ×

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    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, 2021) Guo, Feifei; Estevez Vázquez, Olga; Benedé Ubieto, Raquel; Maya Mile, Douglas; Zheng, Kang; Gallego Durán, Rocío; Rojas Ávalos, Ángela; Ampuero, Javier; Romero Gómez, Manuel; 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; Regueiro, José R.; Liedtke, Christian; Trautwein, Christian; Bañares Cañizares, Rafael; Cubero Palero, Francisco Javier; Benede Ubieto, Raquel; Gómez Del Moral Martín-Consuegra, Manuel María; Vaquero Martín, 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.