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-Vazquez, Olga
A1 Benede-Ubieto, Raquel
A1 Maya-Miles, Douglas
A1 Zheng, Kang
A1 Gallego-Duran, Rocio
A1 Rojas, Angela
A1 Ampuero, Javier
A1 Romero-Gomez, Manuel
A1 Philip, Kaye
A1 Egbuniwe, Isioma U
A1 Chen, Chaobo
A1 Simon, Jorge
A1 Delgado, Teresa C
A1 Martinez-Chantar, Maria Luz
A1 Sun, Jie
A1 Reissing, Johanna
A1 Bruns, Tony
A1 Lamas-Paz, Arantza
A1 Gomez-del-Moral, Manuel
A1 Woitok, Marius Maximilian
A1 Vaquero, Javier
A1 Regueiro, Jose R
A1 Liedtke, Christian
A1 Trautwein, Christian
A1 Bañares, Rafael
A1 Cubero, Francisco Javier
A1 Nevzorova, Yulia A
K1 c-myc
K1 metabolic-associated fatty liver disease (MAFLD)
K1 metformin
K1 oncogene
K1 tumorigenesis
AB 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.
PB MDPI AG
SN 2072-6694
YR 2021
FD 2021-12-31
LK http://hdl.handle.net/10668/20863
UL http://hdl.handle.net/10668/20863
LA en
NO Guo F, Estévez-Vázquez O, Benedé-Ubieto R, Maya-Miles D, Zheng K, Gallego-Durán R, 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 (Basel). 2021 Dec 31;14(1):192.
DS RISalud
RD Apr 6, 2025