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hsa_circ_0004018 suppresses the progression of liver fibrosis through regulating the hsa-miR-660-3p/TEP1 axis
Shan Li1, Fangmin Song2, Xu Lei1
1Department of Infectious Diseases and Lab of Liver Disease, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
Abstract:
Efforts have been made in the prevention and treatment of liver fibrosis. The inhibition or depletion of the hepatic stellate cells (HSCs) has been considered as a potential approach. Recently, there are numbers of studies about the role of the circular RNA in the disease progression. However, the role of circular RNA in the regulation of HSCs and the progression of liver fibrosis remained elusive. In this study, we constructed a CCl4-induced liver fibrosis mouse model and overexpressed hsa_circ_0004018 in HSCs. Then, salvianolic acid B was used to treat HSCs in vitro. We found that hsa_circ_0004018 is downregulated in liver fibrogenesis. Luciferase reporter assay was performed to verify the interaction of hsa_circ_0004018, hsa-miR-660-3p and TEP1. It showed that hsa_circ_0004018 may act as a sponge of hsa-miR-660-3p, which can target and downregulate the expression of TEP1. hsa_circ_0004018 expressing lentivirus was used to investigate the in-vivo function of hsa_circ_0004018 in CCl4-induced liver fibrosis mice. We also reveal that the hsa_circ_0004018/hsa-miR-660-3p/TEP1 axis contributes to the proliferation and activation of HSCs. In addition, the overexpression of hsa_circ_0004018 alleviated the progression of liver fibrosis. In conclusion, our study highlights hsa_circ_0004018 as a potential biomarker and therapeutic target for liver fibrosis.
Insights
This study reveals that hsa_circ_0004018, a circular RNA, is downregulated in liver fibrosis. Overexpressing hsa_circ_0004018 inhibits hepatic stellate cell activation and alleviates liver fibrosis progression.
Area of Science:
- Molecular Biology
- Hepatology
- Biochemistry
Background:
- Liver fibrosis is a significant health concern, and targeting hepatic stellate cells (HSCs) is a key therapeutic strategy.
- The role of circular RNAs (circRNAs) in liver fibrosis and HSC regulation is not fully understood.
- Investigating novel molecular mechanisms is crucial for developing effective liver fibrosis treatments.
Purpose of the Study:
- To elucidate the function of hsa_circ_0004018 in the context of liver fibrosis.
- To determine the regulatory mechanism of hsa_circ_0004018 in HSCs.
- To explore hsa_circ_0004018 as a potential therapeutic target for liver fibrosis.
Main Methods:
- Construction of a carbon tetrachloride (CCl4)-induced liver fibrosis mouse model.
- Overexpression of hsa_circ_0004018 in HSCs in vitro and in vivo using lentivirus.
- Luciferase reporter assays to confirm interactions between hsa_circ_0004018, hsa-miR-660-3p, and TEP1.
Main Results:
- hsa_circ_0004018 expression was found to be downregulated during liver fibrogenesis.
- hsa_circ_0004018 functions as a molecular sponge for hsa-miR-660-3p, inhibiting TEP1 expression.
- The hsa_circ_0004018/hsa-miR-660-3p/TEP1 axis regulates HSC proliferation and activation.
- Overexpression of hsa_circ_0004018 ameliorated liver fibrosis in the mouse model.
Conclusions:
- hsa_circ_0004018 plays a protective role in liver fibrosis by inhibiting HSC activation.
- The hsa_circ_0004018/hsa-miR-660-3p/TEP1 pathway is a critical regulator of liver fibrogenesis.
- hsa_circ_0004018 represents a promising diagnostic biomarker and therapeutic target for liver fibrosis.
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