Comprehensive understanding of context-specific functions of PHF2 in lipid metabolic tissues

Adipose tissue and the liver are known to regulate lipid metabolism through the storage, synthesis, and breakdown of lipids. However, the shared molecular factors affecting lipid metabolism in both tissues remain unclear. Plant Homeodomain Finger 2 (PHF2), one of the histone lysine demethylase7 family, serves as an epigenetic regulator in adipose tissue and E3 ubiquitin ligase in liver cancer. This study uses bioinformatics to analyze the role of PHF2 in lipid metabolism, focusing on its functions in adipose tissue and the liver. We utilized cDNA-chip microarrays, public clinical data, and in vitro three-dimensional cell culture models, validating our bioinformatics findings. Consequently, our analyses showed that PHF2 is positively involved in histone demethylase activity and adipogenesis in patients with obesity and moderate liver disease. However, PHF2 suppressed de novo lipogenesis and tumor progression in patients with liver cancer, enhancing immune cell infiltration in liver cancer. Furthermore, it was experimentally confirmed that PHF2 increases lipid accumulation in adipocytes but acts as a tumor suppressor in liver cancer cells. Overall, this study provides a comprehensive overview of PHF2, highlighting its biological importance.