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Transposable elements-mediated recruitment of KDM1A epigenetically silences HNF4A expression to promote hepatocellular carcinoma.
Jing, Tiantian; Wei, Dianhui; Xu, Xiaoli; Wu, Chengsi; Yuan, Lili; Huang, Yiwen; Liu, Yizhen; Jiang, Yanyi; Wang, Boshi.
Affiliation
  • Jing T; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China.
  • Wei D; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China.
  • Xu X; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China.
  • Wu C; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China.
  • Yuan L; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China.
  • Huang Y; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China.
  • Liu Y; Department of Medical Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. aliuyz@126.com.
  • Jiang Y; Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, China. yanyij@cmpt.ac.cn.
  • Wang B; University of Science and Technology of China, Hefei, 230026, China. yanyij@cmpt.ac.cn.
Nat Commun ; 15(1): 5631, 2024 Jul 04.
Article de En | MEDLINE | ID: mdl-38965210
ABSTRACT
Transposable elements (TEs) contribute to gene expression regulation by acting as cis-regulatory elements that attract transcription factors and epigenetic regulators. This research aims to explore the functional and clinical implications of transposable element-related molecular events in hepatocellular carcinoma, focusing on the mechanism through which liver-specific accessible TEs (liver-TEs) regulate adjacent gene expression. Our findings reveal that the expression of HNF4A is inversely regulated by proximate liver-TEs, which facilitates liver cancer cell proliferation. Mechanistically, liver-TEs are predominantly occupied by the histone demethylase, KDM1A. KDM1A negatively influences the methylation of histone H3 Lys4 (H3K4) of liver-TEs, resulting in the epigenetic silencing of HNF4A expression. The suppression of HNF4A mediated by KDM1A promotes liver cancer cell proliferation. In conclusion, this study uncovers a liver-TE/KDM1A/HNF4A regulatory axis that promotes liver cancer growth and highlights KDM1A as a promising therapeutic target. Our findings provide insight into the transposable element-related molecular mechanisms underlying liver cancer progression.
Sujet(s)

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Éléments transposables d'ADN / Régulation de l'expression des gènes tumoraux / Carcinome hépatocellulaire / Épigenèse génétique / Prolifération cellulaire / Facteur nucléaire hépatocytaire HNF-4 / Histone Demethylases / Tumeurs du foie Limites: Animals / Humans / Male Langue: En Journal: Nat Commun Sujet du journal: BIOLOGIA / CIENCIA Année: 2024 Type de document: Article Pays d'affiliation: Chine Pays de publication: Royaume-Uni

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Éléments transposables d'ADN / Régulation de l'expression des gènes tumoraux / Carcinome hépatocellulaire / Épigenèse génétique / Prolifération cellulaire / Facteur nucléaire hépatocytaire HNF-4 / Histone Demethylases / Tumeurs du foie Limites: Animals / Humans / Male Langue: En Journal: Nat Commun Sujet du journal: BIOLOGIA / CIENCIA Année: 2024 Type de document: Article Pays d'affiliation: Chine Pays de publication: Royaume-Uni