Effect of HNF4α on the Process of Liver Cancer and as a Potential Therapeutic Target

作者：Nachuan Zhang · 发表于：Theoretical and Natural Science · 年份：2024 · DOI：10.54254/2753-8818/2024.la18091 · 研究领域：Liver physiology and pathology、Liver Disease Diagnosis and Treatment、Pancreatic function and diabetes

As a ligand-dependent transcription factor of the nuclear receptor family, HNF4α can be regulated by a variety of pathways, and can also be recruited to the DNA sequence through a variety of pathways to regulate downstream target genes by virtue of its three-dimensional structure. HNF4α is usually enriched in organs such as the liver, gallbladder, pancreas, kidneys, etc., and mutations in the HNF4A gene can cause lesions in these organs, including diseases such as liver cancer. However, the pathological role of HNF4α in different diseases is not well understood. Previous studies have shown that 12 variants of HNF4α are jointly regulated by the P1/P2 promoters. HNF4α can be recruited to specific DNA sequences by intermediates (including MLL4, KAT2B, etc.) through DNA-binding domain (DBD) after ligand-binding domain (LBD) has bound ligands. The review goes on to enumerate several pathways, pathways in which HNF4A expression is regulated, and HNF4α acts on promoters or enhancers to regulate the expression of downstream target genes. KDM1A regulates the HNF4A expression pathway, mutations in HNF1α POU domain to downregulate HNF4A promoter activity and NRF2-mediated STAT3 activation to silence HNF4A expression through miR-4, and the functional differences of different subtypes of HNF4α regulated by P1/P2, and the interaction between HNF4α and HIC1 affects the function of HNF4α in regulating FUF/FDF. This review aims to stimulate further research on HNF4α, and the specific pathogen...