Study on the mechanism of hsa_circ_0074763 regulating the miR-3667-3P/ACSL4 axis in liver fibrosis
Abstract This study aimed to investigate the involvement of hsa_circ_0074763 in the activation of HSCs (hepatic stellate cells ) and liver fibrosis. Additionally, it aimed to conduct a preliminary analysis of the molecular mechanism targeting miR-3667-3p/ACSL4 (Long-chain acyl-CoA synthetase 4), the...
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Nature Portfolio
2025-03-01
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| Online Access: | https://doi.org/10.1038/s41598-025-91393-2 |
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| author | Yanling Cheng Tiantian Song Jiachen Yao Qirong Wang Chunyan Meng Fumin Feng |
| author_facet | Yanling Cheng Tiantian Song Jiachen Yao Qirong Wang Chunyan Meng Fumin Feng |
| author_sort | Yanling Cheng |
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| description | Abstract This study aimed to investigate the involvement of hsa_circ_0074763 in the activation of HSCs (hepatic stellate cells ) and liver fibrosis. Additionally, it aimed to conduct a preliminary analysis of the molecular mechanism targeting miR-3667-3p/ACSL4 (Long-chain acyl-CoA synthetase 4), thereby providing novel molecular targets for liver fibrosis. The GEO database was utilized to identify differentially expressed hsa_circ_0074763 and determined its subcellular localization in LX-2 cells using fluorescence in situ hybridization. Bioinformatics analysis was employed for result prediction, and the interaction between hsa_circ_0074763 and miR-3667-3P was confirmed using dual-luciferase reporter gene assay. ACSL4 mediated ferroptosis was detected with kit. Hsa_circ_0074763 exhibits high expression levels in the fibrosis model. Validation through dual-luciferase reporter gene assays confirms the interaction between hsa_circ_0074763 and miR-3667-3P. Functional cell experiments demonstrate that overexpression of hsa_circ_0074763 promotes proliferation of LX-2 cells, elevates inflammation levels, and inhibits apoptosis. Additionally, ACSL4 has been identified as a direct target of miR-3667-3P, with overexpression of hsa_circ_0074763 counteracting the inhibitory effect on ACSL4 by suppressing miR-3667-3P. Overexpression of ACSL4 increased the expression levels of ROS (Lipid Oxidation), Iron (Ferro Orange) and MDA (Malondialdehyde), and decreased the expression levels of GPX4 (Glutathione peroxidase 4) and GSH (Glutathione). Our finding suggests that overexpression of hsa_circ_0074763 likely enhances the HSC activation through modulation of the miR-3667-3P/ACSL4 axis. Therefore, hsa_circ_0074763 holds potential as a therapeutic target for liver fibrosis. |
| format | Article |
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| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-dbbc68c65ec44e7dafbf8fdb53dc89842025-08-20T03:40:48ZengNature PortfolioScientific Reports2045-23222025-03-0115111410.1038/s41598-025-91393-2Study on the mechanism of hsa_circ_0074763 regulating the miR-3667-3P/ACSL4 axis in liver fibrosisYanling Cheng0Tiantian Song1Jiachen Yao2Qirong Wang3Chunyan Meng4Fumin Feng5School of Public Health, North China University of Science and TechnologySchool of Public Health, North China University of Science and TechnologySchool of Public Health, North China University of Science and TechnologySchool of Public Health, North China University of Science and TechnologySchool of Public Health, North China University of Science and TechnologySchool of Public Health, North China University of Science and TechnologyAbstract This study aimed to investigate the involvement of hsa_circ_0074763 in the activation of HSCs (hepatic stellate cells ) and liver fibrosis. Additionally, it aimed to conduct a preliminary analysis of the molecular mechanism targeting miR-3667-3p/ACSL4 (Long-chain acyl-CoA synthetase 4), thereby providing novel molecular targets for liver fibrosis. The GEO database was utilized to identify differentially expressed hsa_circ_0074763 and determined its subcellular localization in LX-2 cells using fluorescence in situ hybridization. Bioinformatics analysis was employed for result prediction, and the interaction between hsa_circ_0074763 and miR-3667-3P was confirmed using dual-luciferase reporter gene assay. ACSL4 mediated ferroptosis was detected with kit. Hsa_circ_0074763 exhibits high expression levels in the fibrosis model. Validation through dual-luciferase reporter gene assays confirms the interaction between hsa_circ_0074763 and miR-3667-3P. Functional cell experiments demonstrate that overexpression of hsa_circ_0074763 promotes proliferation of LX-2 cells, elevates inflammation levels, and inhibits apoptosis. Additionally, ACSL4 has been identified as a direct target of miR-3667-3P, with overexpression of hsa_circ_0074763 counteracting the inhibitory effect on ACSL4 by suppressing miR-3667-3P. Overexpression of ACSL4 increased the expression levels of ROS (Lipid Oxidation), Iron (Ferro Orange) and MDA (Malondialdehyde), and decreased the expression levels of GPX4 (Glutathione peroxidase 4) and GSH (Glutathione). Our finding suggests that overexpression of hsa_circ_0074763 likely enhances the HSC activation through modulation of the miR-3667-3P/ACSL4 axis. Therefore, hsa_circ_0074763 holds potential as a therapeutic target for liver fibrosis.https://doi.org/10.1038/s41598-025-91393-2CircRNAMiRNALiver fibrosisFerroptosis |
| spellingShingle | Yanling Cheng Tiantian Song Jiachen Yao Qirong Wang Chunyan Meng Fumin Feng Study on the mechanism of hsa_circ_0074763 regulating the miR-3667-3P/ACSL4 axis in liver fibrosis Scientific Reports CircRNA MiRNA Liver fibrosis Ferroptosis |
| title | Study on the mechanism of hsa_circ_0074763 regulating the miR-3667-3P/ACSL4 axis in liver fibrosis |
| title_full | Study on the mechanism of hsa_circ_0074763 regulating the miR-3667-3P/ACSL4 axis in liver fibrosis |
| title_fullStr | Study on the mechanism of hsa_circ_0074763 regulating the miR-3667-3P/ACSL4 axis in liver fibrosis |
| title_full_unstemmed | Study on the mechanism of hsa_circ_0074763 regulating the miR-3667-3P/ACSL4 axis in liver fibrosis |
| title_short | Study on the mechanism of hsa_circ_0074763 regulating the miR-3667-3P/ACSL4 axis in liver fibrosis |
| title_sort | study on the mechanism of hsa circ 0074763 regulating the mir 3667 3p acsl4 axis in liver fibrosis |
| topic | CircRNA MiRNA Liver fibrosis Ferroptosis |
| url | https://doi.org/10.1038/s41598-025-91393-2 |
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