LncRNA-MIAT activates hepatic stellate cells via regulating Hippo pathway and epithelial-to-mesenchymal transition
Abstract Long non-coding RNA-myocardial infarction-associated transcript (lncRNA-MIAT) has been reported to play an important role in the development of multiple cancers. However, the biological roles of MIAT in liver fibrosis are still unknown. In this study, the expression of MIAT is up-regulated...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-03-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-04670-z |
| _version_ | 1827388225089437696 |
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| author | Yating Zhan Qiqi Tao Qishan Meng Rongrong Zhang Lifan Lin Xinmiao Li Lei Zheng Jianjian Zheng |
| author_facet | Yating Zhan Qiqi Tao Qishan Meng Rongrong Zhang Lifan Lin Xinmiao Li Lei Zheng Jianjian Zheng |
| author_sort | Yating Zhan |
| collection | DOAJ |
| description | Abstract Long non-coding RNA-myocardial infarction-associated transcript (lncRNA-MIAT) has been reported to play an important role in the development of multiple cancers. However, the biological roles of MIAT in liver fibrosis are still unknown. In this study, the expression of MIAT is up-regulated during liver fibrosis. Silencing MIAT leads to the suppression of hepatic stellate cell (HSC) proliferation and collagen expression. Double immunofluorescence analysis additionally demonstrates that MIAT inhibition leads to the suppression of type I collagen and α-SMA in vitro. In vivo, MIAT knockdown contributes to the inhibition of fibrosis progression and collagen accumulation. MIAT is confirmed as a target of miR-3085-5p, and the co-location of MIAT and miR-3085-5p is found in HSC cytoplasm. Interestingly, there is a negative correlation between MIAT expression and miR-3085-5p level in cirrhotic patients as well as activated HSCs. In addition, the effects of MIAT inhibition on HSC inactivation are blocked down by miR-3085-5p inhibitor. YAP is a target of miR-3085-5p. Reduced YAP caused by loss of MIAT is reversed by miR-3085-5p inhibitor. Notably, YAP knockdown results in the suppression of MIAT-mediated epithelial-to-mesenchymal transition (EMT) process. In conclusion, we demonstrate that MIAT enhances the activation of HSCs, at least in part, via miR-3085-5p/YAP/EMT signaling pathway. |
| first_indexed | 2024-03-08T16:14:23Z |
| format | Article |
| id | doaj.art-71bfb92c00fb41159696c81ccc2edb13 |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-08T16:14:23Z |
| publishDate | 2023-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-71bfb92c00fb41159696c81ccc2edb132024-01-07T12:39:44ZengNature PortfolioCommunications Biology2399-36422023-03-016111110.1038/s42003-023-04670-zLncRNA-MIAT activates hepatic stellate cells via regulating Hippo pathway and epithelial-to-mesenchymal transitionYating Zhan0Qiqi Tao1Qishan Meng2Rongrong Zhang3Lifan Lin4Xinmiao Li5Lei Zheng6Jianjian Zheng7Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical UniversityKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical UniversityKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical UniversityKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical UniversityKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical UniversityKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical UniversityKey Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical UniversityKey Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical UniversityAbstract Long non-coding RNA-myocardial infarction-associated transcript (lncRNA-MIAT) has been reported to play an important role in the development of multiple cancers. However, the biological roles of MIAT in liver fibrosis are still unknown. In this study, the expression of MIAT is up-regulated during liver fibrosis. Silencing MIAT leads to the suppression of hepatic stellate cell (HSC) proliferation and collagen expression. Double immunofluorescence analysis additionally demonstrates that MIAT inhibition leads to the suppression of type I collagen and α-SMA in vitro. In vivo, MIAT knockdown contributes to the inhibition of fibrosis progression and collagen accumulation. MIAT is confirmed as a target of miR-3085-5p, and the co-location of MIAT and miR-3085-5p is found in HSC cytoplasm. Interestingly, there is a negative correlation between MIAT expression and miR-3085-5p level in cirrhotic patients as well as activated HSCs. In addition, the effects of MIAT inhibition on HSC inactivation are blocked down by miR-3085-5p inhibitor. YAP is a target of miR-3085-5p. Reduced YAP caused by loss of MIAT is reversed by miR-3085-5p inhibitor. Notably, YAP knockdown results in the suppression of MIAT-mediated epithelial-to-mesenchymal transition (EMT) process. In conclusion, we demonstrate that MIAT enhances the activation of HSCs, at least in part, via miR-3085-5p/YAP/EMT signaling pathway.https://doi.org/10.1038/s42003-023-04670-z |
| spellingShingle | Yating Zhan Qiqi Tao Qishan Meng Rongrong Zhang Lifan Lin Xinmiao Li Lei Zheng Jianjian Zheng LncRNA-MIAT activates hepatic stellate cells via regulating Hippo pathway and epithelial-to-mesenchymal transition Communications Biology |
| title | LncRNA-MIAT activates hepatic stellate cells via regulating Hippo pathway and epithelial-to-mesenchymal transition |
| title_full | LncRNA-MIAT activates hepatic stellate cells via regulating Hippo pathway and epithelial-to-mesenchymal transition |
| title_fullStr | LncRNA-MIAT activates hepatic stellate cells via regulating Hippo pathway and epithelial-to-mesenchymal transition |
| title_full_unstemmed | LncRNA-MIAT activates hepatic stellate cells via regulating Hippo pathway and epithelial-to-mesenchymal transition |
| title_short | LncRNA-MIAT activates hepatic stellate cells via regulating Hippo pathway and epithelial-to-mesenchymal transition |
| title_sort | lncrna miat activates hepatic stellate cells via regulating hippo pathway and epithelial to mesenchymal transition |
| url | https://doi.org/10.1038/s42003-023-04670-z |
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