Overexpression of ring finger protein 20 inhibits the progression of liver fibrosis via mediation of histone H2B lysine 120 ubiquitination


Liver fibrosis is a chronic liver injury that leads to liver cirrhosis and liver cancer. Ring finger protein 20 (RNF20), also named as E3 ubiquitin-protein ligase BRE1A, has been reported to be involved in chronic liver diseases. However, the role of RNF20 in liver fibrosis remains unclear. To mimic liver fibrosis in vitro, LX-2 cells were treated with TGF-β. Gene and protein expressions were detected by RT-qPCR and western blot, respectively. The mechanism by which RNF20 mediated the progression of liver fibrosis was explored by bioinformatics analysis. Finally, in vivo mouse model of liver fibrosis was established to detect the function of RNF20. The results indicated that TGF-β-induced increase of cell viability and migration was significantly reversed by RNF20 overexpression. Consistently, overexpression of RNF20 significantly reversed TGF-β-induced activation of fibrotic proteins in LX-2 cells. Meanwhile, VEGFA, TNF-α and IL-6 were found to be the downstream targets of RNF20 in LX-2 cells. Moreover, RNF20 overexpression notably inhibited the progression of liver fibrosis via ubiquitination of H2B. Finally, RNF20 upregulation significantly attenuated the symptom of liver fibrosis in vivo. In summary, overexpression of RNF20 significantly inhibited the progression of liver fibrosis in vitro and in vivo. Therefore, RNF20 might serve as a new target for the treatment of liver fibrosis.

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The study was supported by the National Natural Science Foundation of China (No. 81672115).

Author information




HH design study and revised the manuscript; SC and XD analysis data and perform manuscript drafting; HL, YG and YZ search the literature and collect data; HH reviewed the results and made critical comments on the manuscript.

Corresponding author

Correspondence to Haijun Huang.

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These authors declared no competing interests in this research.

Ethical approval

In vivo study, all the protocols were performed according to the guidelines of the Use Committee of Zhejiang Provincial People’s Hospital (No. 20200004), and all the animal experiments were performed in accordance with National Institutes of Health guide for the care and use of laboratory animals. The clinical samples were collected in accordance with the Institutional Ethical Committee of Zhejiang Provincial People’s Hospital.

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Chen, S., Dai, X., Li, H. et al. Overexpression of ring finger protein 20 inhibits the progression of liver fibrosis via mediation of histone H2B lysine 120 ubiquitination. Human Cell (2021). https://doi.org/10.1007/s13577-021-00498-z

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  • Liver fibrosis
  • RNF20
  • H2BK120ub
  • Ubiquitination