Hamdy Hayam, Shen Chang, Xu Jiashun, Fan Die, Zhang Yiwen, Li Hui, Wei Yonglong, Sun Jianwei
Yunnan Key Laboratory of Cell Metabolism and Diseases, Center for Life Sciences, School of Life Sciences, The Affiliated Hospital of Yunnan University, Yunnan University, Kunming, China.
Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, New Valley University, New Valley, Egypt.
Cell Oncol (Dordr). 2025 Aug;48(4):885-897. doi: 10.1007/s13402-025-01064-7. Epub 2025 May 20.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, associated with viral hepatitis, alcohol consumption, and non-alcoholic fatty liver disease. Hepatocyte nuclear factor 4 alpha (HNF4α), a crucial transcription factor for liver function (glucose and lipid metabolism, bile acid homeostasis, and cellular differentiation), is often dysregulated in HCC progression. This review provides a comprehensive overview of the role of HNF4α in hepatic oncogenesis, providing novel inshight into its regulatory effects on epithelial-mesenchymal transition (EMT), metabolic alterations (including the Warburg effect), cell cycle control, and tumor microenvironment. We also discuss therapeutic strategies targeting HNF4α focusing on restoring metabolic balance and inducing apoptosis. This integrated analysis advances our understanding of HNF4α's contribution to HCC and may pave the way for the development of targeted therapies (Fig. 1).
肝细胞癌（HCC）是癌症相关死亡的主要原因，与病毒性肝炎、酒精摄入和非酒精性脂肪性肝病有关。肝细胞核因子4α（HNF4α）是肝功能（葡萄糖和脂质代谢、胆汁酸稳态和细胞分化）的关键转录因子，在HCC进展过程中常发生失调。本综述全面概述了HNF4α在肝脏肿瘤发生中的作用，为其对上皮-间质转化（EMT）、代谢改变（包括瓦伯格效应）、细胞周期控制和肿瘤微环境的调节作用提供了新的见解。我们还讨论了针对HNF4α的治疗策略，重点是恢复代谢平衡和诱导细胞凋亡。这种综合分析增进了我们对HNF4α对HCC贡献的理解，并可能为靶向治疗的发展铺平道路（图1）。
