CircLDLR acts as a sponge for miR-667-5p to regulate SIRT1 expression in non-alcoholic fatty liver disease
Abstract Background Non-alcoholic fatty liver (NAFLD) is a complex metabolic disease characterized by fatty degeneration of hepatocytes. Circular RNAs (circRNAs) have been reported to be essential for (NAFLD progression. The potential mechanism of circRNA low-density lipoprotein receptor (circLDLR)...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | Lipids in Health and Disease |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12944-022-01740-9 |
| _version_ | 1811310982773866496 |
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| author | Xinlu Yuan Yanyan Li Song Wen Chenglin Xu Congcong Wang Yanju He Ligang Zhou |
| author_facet | Xinlu Yuan Yanyan Li Song Wen Chenglin Xu Congcong Wang Yanju He Ligang Zhou |
| author_sort | Xinlu Yuan |
| collection | DOAJ |
| description | Abstract Background Non-alcoholic fatty liver (NAFLD) is a complex metabolic disease characterized by fatty degeneration of hepatocytes. Circular RNAs (circRNAs) have been reported to be essential for (NAFLD progression. The potential mechanism of circRNA low-density lipoprotein receptor (circLDLR) in the NAFLD was investigated in this study. Methods Hepatocyte (Hepa1-6) cells treated with oleic acid/palmitic acid (OA/PA) were used as the in vitro NAFLD model, and C57BL/6 mice fed with high-fat diet (HFD) were used as the in vivo NAFLD model. The circLDLR, LDLR, and miR-667-5p expression were measured by quantitative real-time polymerase chain reaction (qRT-PCR), while the protein levels of Light Chain Microtubule-Associated Protein 3 (LC3) and Sequestosome-1(p62) was examined by western blot. The circLDLR location was confirmed using RNA fluorescence in situ hybridization. Oil red O staining was carried out to measure lipid deposition in cells. The secreted levels of triglyceride (TG) and total cholesterol (TC) were detected through Enzymatic. The existence of the circLDLR/miR-667-5p/sirtuin 1 (SIRT1) regulatory axis was validated by applying the dual-luciferase reporter assay. Results The circLDLR expression showed a prominent down-regulation in OA/PA-treated Hepa1-6 cells, whereas the LDLR expression was up-regulated. Overexpression of circLDLR significantly attenuated lipid droplet accumulation in NAFLD models in vitro/vivo, reduced TG, TC, and p62 levels, and increased LC3-II levels and the amount of the green fluorescent protein (GFP)-LC3 puncta in cells. CircLDLR and SIRT1 are common targets of miR-667-5p to inhibit the TG and TC and promote the autophagy pathway. SIRT1 knockdown reversed the effects of circLDLR overexpression. Conclusions CircLDLR alleviated the development of NAFLD by inducing autophagic flux while modulating the miR-667-5p/SIRT1 axis reversed its effects, suggesting that targeting circLDLR/miR-667-5p/SIRT1 axis may be a promising therapeutic strategy for NAFLD. |
| first_indexed | 2024-04-13T10:08:40Z |
| format | Article |
| id | doaj.art-89b87d21513d42eb897330efed01c757 |
| institution | Directory Open Access Journal |
| issn | 1476-511X |
| language | English |
| last_indexed | 2024-04-13T10:08:40Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
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| series | Lipids in Health and Disease |
| spelling | doaj.art-89b87d21513d42eb897330efed01c7572022-12-22T02:50:59ZengBMCLipids in Health and Disease1476-511X2022-11-0121111510.1186/s12944-022-01740-9CircLDLR acts as a sponge for miR-667-5p to regulate SIRT1 expression in non-alcoholic fatty liver diseaseXinlu Yuan0Yanyan Li1Song Wen2Chenglin Xu3Congcong Wang4Yanju He5Ligang Zhou6Department of Endocrinology and Metabolic Diseases, Shanghai Pudong Hospital, Fudan University Pudong Medical CenterDepartment of Endocrinology and Metabolic Diseases, Shanghai Pudong Hospital, Fudan University Pudong Medical CenterDepartment of Endocrinology and Metabolic Diseases, Shanghai Pudong Hospital, Fudan University Pudong Medical CenterDepartment of Endocrinology and Metabolic Diseases, Shanghai Pudong Hospital, Fudan University Pudong Medical CenterDepartment of Endocrinology and Metabolic Diseases, Shanghai Pudong Hospital, Fudan University Pudong Medical CenterDepartment of Endocrinology and Metabolic Diseases, Shanghai Pudong Hospital, Fudan University Pudong Medical CenterDepartment of Endocrinology and Metabolic Diseases, Shanghai Pudong Hospital, Fudan University Pudong Medical CenterAbstract Background Non-alcoholic fatty liver (NAFLD) is a complex metabolic disease characterized by fatty degeneration of hepatocytes. Circular RNAs (circRNAs) have been reported to be essential for (NAFLD progression. The potential mechanism of circRNA low-density lipoprotein receptor (circLDLR) in the NAFLD was investigated in this study. Methods Hepatocyte (Hepa1-6) cells treated with oleic acid/palmitic acid (OA/PA) were used as the in vitro NAFLD model, and C57BL/6 mice fed with high-fat diet (HFD) were used as the in vivo NAFLD model. The circLDLR, LDLR, and miR-667-5p expression were measured by quantitative real-time polymerase chain reaction (qRT-PCR), while the protein levels of Light Chain Microtubule-Associated Protein 3 (LC3) and Sequestosome-1(p62) was examined by western blot. The circLDLR location was confirmed using RNA fluorescence in situ hybridization. Oil red O staining was carried out to measure lipid deposition in cells. The secreted levels of triglyceride (TG) and total cholesterol (TC) were detected through Enzymatic. The existence of the circLDLR/miR-667-5p/sirtuin 1 (SIRT1) regulatory axis was validated by applying the dual-luciferase reporter assay. Results The circLDLR expression showed a prominent down-regulation in OA/PA-treated Hepa1-6 cells, whereas the LDLR expression was up-regulated. Overexpression of circLDLR significantly attenuated lipid droplet accumulation in NAFLD models in vitro/vivo, reduced TG, TC, and p62 levels, and increased LC3-II levels and the amount of the green fluorescent protein (GFP)-LC3 puncta in cells. CircLDLR and SIRT1 are common targets of miR-667-5p to inhibit the TG and TC and promote the autophagy pathway. SIRT1 knockdown reversed the effects of circLDLR overexpression. Conclusions CircLDLR alleviated the development of NAFLD by inducing autophagic flux while modulating the miR-667-5p/SIRT1 axis reversed its effects, suggesting that targeting circLDLR/miR-667-5p/SIRT1 axis may be a promising therapeutic strategy for NAFLD.https://doi.org/10.1186/s12944-022-01740-9Non-alcoholic fatty liver diseasecircRNAsSIRT1miR-667-5pAutophagy |
| spellingShingle | Xinlu Yuan Yanyan Li Song Wen Chenglin Xu Congcong Wang Yanju He Ligang Zhou CircLDLR acts as a sponge for miR-667-5p to regulate SIRT1 expression in non-alcoholic fatty liver disease Lipids in Health and Disease Non-alcoholic fatty liver disease circRNAs SIRT1 miR-667-5p Autophagy |
| title | CircLDLR acts as a sponge for miR-667-5p to regulate SIRT1 expression in non-alcoholic fatty liver disease |
| title_full | CircLDLR acts as a sponge for miR-667-5p to regulate SIRT1 expression in non-alcoholic fatty liver disease |
| title_fullStr | CircLDLR acts as a sponge for miR-667-5p to regulate SIRT1 expression in non-alcoholic fatty liver disease |
| title_full_unstemmed | CircLDLR acts as a sponge for miR-667-5p to regulate SIRT1 expression in non-alcoholic fatty liver disease |
| title_short | CircLDLR acts as a sponge for miR-667-5p to regulate SIRT1 expression in non-alcoholic fatty liver disease |
| title_sort | circldlr acts as a sponge for mir 667 5p to regulate sirt1 expression in non alcoholic fatty liver disease |
| topic | Non-alcoholic fatty liver disease circRNAs SIRT1 miR-667-5p Autophagy |
| url | https://doi.org/10.1186/s12944-022-01740-9 |
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