表观遗传学
DNA甲基化
生物
肝细胞癌
组蛋白
转座因子
癌症研究
脱甲基酶
肝癌
基因沉默
基因表达调控
基因表达
基因
细胞生物学
遗传学
基因组
作者
Tiantian Jing,Dianhui Wei,Xiaoli Xu,Chengsi Wu,Lili Yuan,Yiwen Huang,Yizhen Liu,Yan-Yi Jiang,Boshi Wang
标识
DOI:10.1038/s41467-024-49926-2
摘要
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.
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