Rah Bilal, Farhat Nada Mazen, Hamad Mawieh, Muhammad Jibran Sualeh
Iron Biology Group, Research Institute of Medical & Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, P.O. Box 27272, Sharjah, United Arab Emirates.
Clin Exp Med. 2023 Nov;23(7):3147-3157. doi: 10.1007/s10238-023-01047-8. Epub 2023 Mar 28.
Iron metabolism plays a crucial role in the development and progression of hepatocellular carcinoma (HCC), the most common type of primary liver cancer. Iron is an essential micronutrient that is involved in many physiological processes, including oxygen transport, DNA synthesis, and cellular growth and differentiation. However, excessive iron accumulation in the liver has been linked to oxidative stress, inflammation, and DNA damage, which can increase the risk of HCC. Studies have shown that iron overload is common in patients with HCC and that it is associated with a poor prognosis and reduced survival rates. Various iron metabolism-related proteins and signaling pathways such as the JAK/STAT pathway are dysregulated in HCC. Moreover, reduced hepcidin expression was reported to promote HCC in a JAK/STAT pathway-dependent manner. Therefore, it is important to understand the crosstalk between iron metabolism and the JAK/STAT pathway to prevent or treat iron overload in HCC. Iron chelators can bind to iron and remove it from the body, but its effect on JAK/STAT pathway is unclear. Also, HCC can be targeted by using the JAK/STAT pathway inhibitors, but their effect on hepatic iron metabolism is not known. In this review, for the first time, we focus on the role of the JAK/STAT signaling pathway in regulating cellular iron metabolism and its association with the development of HCC. We also discuss novel pharmacological agents and their therapeutic potential in manipulating iron metabolism and JAK/STAT signaling in HCC.
铁代谢在肝细胞癌（HCC，最常见的原发性肝癌类型）的发生和发展中起着关键作用。铁是一种必需的微量营养素，参与许多生理过程，包括氧气运输、DNA合成以及细胞生长和分化。然而，肝脏中过量的铁积累与氧化应激、炎症和DNA损伤有关，这会增加患肝细胞癌的风险。研究表明，铁过载在肝细胞癌患者中很常见，并且与预后不良和生存率降低有关。各种与铁代谢相关的蛋白质和信号通路，如JAK/STAT通路，在肝细胞癌中失调。此外，据报道，铁调素表达降低以JAK/STAT通路依赖的方式促进肝细胞癌。因此，了解铁代谢与JAK/STAT通路之间的相互作用对于预防或治疗肝细胞癌中的铁过载很重要。铁螯合剂可以与铁结合并将其从体内清除，但其对JAK/STAT通路的影响尚不清楚。此外，可以使用JAK/STAT通路抑制剂靶向肝细胞癌，但其对肝脏铁代谢的影响尚不清楚。在本综述中，我们首次关注JAK/STAT信号通路在调节细胞铁代谢中的作用及其与肝细胞癌发生的关联。我们还讨论了新型药物制剂及其在调节肝细胞癌中铁代谢和JAK/STAT信号传导方面的治疗潜力。
