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- Title
Transposable elements-mediated recruitment of KDM1A epigenetically silences HNF4A expression to promote hepatocellular carcinoma.
- Authors
Jing, Tiantian; Wei, Dianhui; Xu, Xiaoli; Wu, Chengsi; Yuan, Lili; Huang, Yiwen; Liu, Yizhen; Jiang, Yanyi; Wang, Boshi
- 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. 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.
- Subjects
HEPATOCELLULAR carcinoma; GENE expression; GENETIC regulation; CANCER cell proliferation; LIVER cancer; LIVER regeneration
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-49926-2