转座元件 (TE) 作为吸引转录因子和表观遗传调节因子的顺式调节元件，有助于基因表达调节。本研究旨在探讨转座元件相关分子事件在肝细胞癌中的功能和临床意义，重点研究肝脏特异性可及TE（liver-TE）调节邻近基因表达的机制。我们的研究结果表明，HNF4A 的表达受到邻近肝脏 TE 的反向调节，从而促进肝癌细胞增殖。从机制上讲，肝脏 TE 主要被组蛋白去甲基化酶 KDM1A 占据。 KDM1A 对肝脏 TE 的组蛋白 H3 Lys4 (H3K4) 甲基化产生负面影响，导致 HNF4A 表达的表观遗传沉默。 KDM1A 介导的 HNF4A 抑制可促进肝癌细胞增殖。总之，这项研究揭示了促进肝癌生长的肝脏-TE/KDM1A/HNF4A 调节轴，并强调 KDM1A 作为一个有前途的治疗靶点。我们的研究结果提供了对肝癌进展的转座元件相关分子机制的深入了解。© 2024。作者。

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.© 2024. The Author(s).