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

Do-Won Jeong, Jeong-Eun Yun, Kyoung-Hwa Lee, Geon Ho Moon, Ki Yong Hong, Jong-Wan Park, Junji Fukuda, Yong-Seok Lee, Yang-Sook Chun
Author Information
  1. Do-Won Jeong: Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
  2. Jeong-Eun Yun: Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
  3. Kyoung-Hwa Lee: Songdo Bio-Engineering, Incheon Jaeneung University, Incheon, 21987, Republic of Korea.
  4. Geon Ho Moon: Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
  5. Ki Yong Hong: Department of Plastic and Reconstructive Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
  6. Jong-Wan Park: Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. ORCID
  7. Junji Fukuda: Faculty of Engineering, Yokohama National University, Yokohama, 240-8501, Japan. ORCID
  8. Yong-Seok Lee: Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
  9. Yang-Sook Chun: Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. chunys@snu.ac.kr. ORCID

Abstract

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.

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Grants

  1. 2018R1A5A202596423/National Research Foundation of Korea (NRF)
  2. 2019R1A2C208388615/National Research Foundation of Korea (NRF)
  3. RS-2024-00344706/Ministry of Science, ICT and Future Planning (MSIP)
  4. RS-2024-00458826/Ministry of Science, ICT and Future Planning (MSIP)

MeSH Term

Humans
Lipid Metabolism
Liver Neoplasms
Adipose Tissue
Adipogenesis
Liver
Homeodomain Proteins
Lipogenesis
Transcription Factors
Histone Demethylases
Obesity
Animals
Adipocytes
Mice

Chemicals

PHF2 protein, human
Homeodomain Proteins
Transcription Factors
Histone Demethylases

Word Cloud

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