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Transposable elements-mediated recruitment of KDM1A epigenetically silences HNF4A expression to promote hepatocellular carcinoma

文献类型：期刊论文

作者Jing, Tiantian1; Wei, Dianhui1; Xu, Xiaoli1; Wu, Chengsi1; Yuan, Lili1; Huang, Yiwen1; Liu, Yizhen4,5; Jiang, Yanyi2,3; Wang, Boshi1
刊名NATURE COMMUNICATIONS
出版日期2024-07-04
卷号15
DOI10.1038/s41467-024-49926-2
通讯作者Liu, Yizhen(aliuyz@126.com) ; Jiang, Yanyi(yanyij@cmpt.ac.cn) ; Wang, Boshi(wbs137@shsci.org)
英文摘要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. The functional role of transposable elements (TEs) in hepatocellular carcinoma (HCC) remains to be explored. Here, the authors identify a liver-TE/KDM1A/HNF4A regulatory axis that promotes HCC growth and suggest therapeutic targeting of KDM1A.
WOS关键词GENE ACTIVATION ; DEMETHYLASE 1 ; LSD1 ; CELLS ; PROTEINS ; COREST
资助项目National Natural Science Foundation of China[82372737] ; National Natural Science Foundation of China[82203441] ; National Natural Science Foundation of China[82273283] ; National Natural Science Foundation of China[82172905] ; National Natural Science Foundation of China[81972209] ; National Natural Science Foundation of China[82060041] ; National Natural Science Foundation of China[82303079] ; Shanghai Natural Science Foundation[21ZR1461500]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:001263157400017
出版者NATURE PORTFOLIO
资助机构National Natural Science Foundation of China ; Shanghai Natural Science Foundation
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/137009]  
专题中国科学院合肥物质科学研究院
通讯作者Liu, Yizhen; Jiang, Yanyi; Wang, Boshi
作者单位1.Shanghai Jiao Tong Univ, Renji Hosp, Shanghai Canc Inst, State Key Lab Syst Med Canc,Sch Med, Shanghai 200032, Peoples R China
2.Chinese Acad Sci, Inst Hlth & Med Technol, Hefei Inst Phys Sci, Hefei 230031, Peoples R China
3.Univ Sci & Technol China, Hefei 230026, Peoples R China
4.Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China
5.Fudan Univ, Shanghai Canc Ctr, Dept Med Oncol, Shanghai 200032, Peoples R China
推荐引用方式
GB/T 7714		 Jing, Tiantian,Wei, Dianhui,Xu, Xiaoli,et al. Transposable elements-mediated recruitment of KDM1A epigenetically silences HNF4A expression to promote hepatocellular carcinoma[J]. NATURE COMMUNICATIONS,2024,15.
APA Jing, Tiantian.,Wei, Dianhui.,Xu, Xiaoli.,Wu, Chengsi.,Yuan, Lili.,...&Wang, Boshi.(2024).Transposable elements-mediated recruitment of KDM1A epigenetically silences HNF4A expression to promote hepatocellular carcinoma.NATURE COMMUNICATIONS,15.
MLA Jing, Tiantian,et al."Transposable elements-mediated recruitment of KDM1A epigenetically silences HNF4A expression to promote hepatocellular carcinoma".NATURE COMMUNICATIONS 15(2024).

入库方式： OAI收割

来源：合肥物质科学研究院

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