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

Author

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  • Tiantian Jing

    (Shanghai Jiao Tong University School of Medicine)

  • Dianhui Wei

    (Shanghai Jiao Tong University School of Medicine)

  • Xiaoli Xu

    (Shanghai Jiao Tong University School of Medicine)

  • Chengsi Wu

    (Shanghai Jiao Tong University School of Medicine)

  • Lili Yuan

    (Shanghai Jiao Tong University School of Medicine)

  • Yiwen Huang

    (Shanghai Jiao Tong University School of Medicine)

  • Yizhen Liu

    (Fudan University)

  • Yanyi Jiang

    (Chinese Academy of Sciences
    University of Science and Technology of China)

  • Boshi Wang

    (Shanghai Jiao Tong University School of Medicine)

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.

Suggested Citation

  • Tiantian Jing & Dianhui Wei & Xiaoli Xu & Chengsi Wu & Lili Yuan & Yiwen Huang & Yizhen Liu & Yanyi Jiang & Boshi Wang, 2024. "Transposable elements-mediated recruitment of KDM1A epigenetically silences HNF4A expression to promote hepatocellular carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49926-2
    DOI: 10.1038/s41467-024-49926-2
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