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全面了解PHF2在脂质代谢组织中的特定背景功能。

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

作者信息

Jeong Do-Won, Yun Jeong-Eun, Lee Kyoung-Hwa, Moon Geon Ho, Hong Ki Yong, Park Jong-Wan, Fukuda Junji, Lee Yong-Seok, Chun Yang-Sook

机构信息

Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Department of Physiology, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.

出版信息

Sci Rep. 2025 Mar 17;15(1):9074. doi: 10.1038/s41598-025-93438-y.

DOI:10.1038/s41598-025-93438-y
PMID:40097484
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11914216/
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.

摘要

众所周知，脂肪组织和肝脏通过脂质的储存、合成和分解来调节脂质代谢。然而，影响这两种组织脂质代谢的共同分子因素仍不清楚。植物同源结构域指蛋白2（PHF2）是组蛋白赖氨酸去甲基化酶7家族成员之一，在脂肪组织中作为表观遗传调节因子，在肝癌中作为E3泛素连接酶。本研究利用生物信息学分析PHF2在脂质代谢中的作用，重点关注其在脂肪组织和肝脏中的功能。我们使用了cDNA芯片微阵列、公开临床数据和体外三维细胞培养模型，验证了我们的生物信息学研究结果。因此，我们的分析表明，PHF2在肥胖和中度肝病患者中正向参与组蛋白去甲基化酶活性和脂肪生成。然而，PHF2抑制肝癌患者的从头脂肪生成和肿瘤进展，增强肝癌中的免疫细胞浸润。此外，实验证实PHF2增加脂肪细胞中的脂质积累，但在肝癌细胞中起肿瘤抑制作用。总体而言，本研究全面概述了PHF2，突出了其生物学重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d96/11914216/221404c5202b/41598_2025_93438_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d96/11914216/5c1ee6b37e49/41598_2025_93438_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d96/11914216/0f629a56a821/41598_2025_93438_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d96/11914216/f6e6a297fa54/41598_2025_93438_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d96/11914216/d40b2b971019/41598_2025_93438_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d96/11914216/1b86648036e3/41598_2025_93438_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d96/11914216/5d8590021a66/41598_2025_93438_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d96/11914216/2d0e9ef4c40f/41598_2025_93438_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d96/11914216/221404c5202b/41598_2025_93438_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d96/11914216/5c1ee6b37e49/41598_2025_93438_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d96/11914216/0f629a56a821/41598_2025_93438_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d96/11914216/f6e6a297fa54/41598_2025_93438_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d96/11914216/d40b2b971019/41598_2025_93438_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d96/11914216/1b86648036e3/41598_2025_93438_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d96/11914216/5d8590021a66/41598_2025_93438_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d96/11914216/2d0e9ef4c40f/41598_2025_93438_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d96/11914216/221404c5202b/41598_2025_93438_Fig8_HTML.jpg

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