Free fatty acid-induced DDX3 inhibits autophagy via miR-141 upregulation in diet-induced MASLD mice model system
Introduction and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the primary causes of chronic liver disease and may lead to liver cirrhosis and hepatocellular carcinoma. Recent reports suggested that DEAD-box RNA helicase (DDX3) acts as a sensor of free fat ac...
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Elsevier
2025-01-01
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| Series: | Annals of Hepatology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1665268124005416 |
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| author | Md. Musa Hossain Amit K. Mishra Ajay K. Yadav Md. Ismail Teja Naveen Sata Amrendra K. Sah Arnab Banik Gopal Sharma Senthil K. Venugopal |
| author_facet | Md. Musa Hossain Amit K. Mishra Ajay K. Yadav Md. Ismail Teja Naveen Sata Amrendra K. Sah Arnab Banik Gopal Sharma Senthil K. Venugopal |
| author_sort | Md. Musa Hossain |
| collection | DOAJ |
| description | Introduction and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the primary causes of chronic liver disease and may lead to liver cirrhosis and hepatocellular carcinoma. Recent reports suggested that DEAD-box RNA helicase (DDX3) acts as a sensor of free fat accumulation and may modulate the pathogenesis via miRNAs. Hence, we hypothesized that DDX3 might modulate MASLD progression via miRNA-141-mediated inhibition of Sirt-1 and autophagy. Materials and Methods: RNA and total protein were isolated from free fatty acid-treated HepG2 cells or CDAA-fed C57BL/6 mice (6 mice per group) for 6, 18, 32, or 54 weeks. The cells were transfected with DDX3 or miR-141 or siRNA to DDX3, and Western blots for autophagy markers were performed. Results: The FFAs induced the DDX3 and miRNA-141 expression, while downregulating Sirt-1, beclin-1, Atg7, and LC3-II. Overexpression of DDX3 resulted in increased miRNA-141. Overexpression of DDX3 or miRNA-141 downregulated Sirt-1 expression and autophagy marker proteins, while these effects were reversed with siRNA to DDX3. The expression of both DDX3 and miRNA-141 was significantly increased, while autophagy markers were downregulated in CDAA-fed mice. Conclusions: These results confirmed that FFA-induced DDX3 induced the expression of miRNA-141, which in turn targeted Sirt-1 and decreased autophagy. |
| format | Article |
| id | doaj-art-936fa91ccc4f41e89b60e1f21aa61ee3 |
| institution | OA Journals |
| issn | 1665-2681 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Annals of Hepatology |
| spelling | doaj-art-936fa91ccc4f41e89b60e1f21aa61ee32025-08-20T02:04:49ZengElsevierAnnals of Hepatology1665-26812025-01-0130110175810.1016/j.aohep.2024.101758Free fatty acid-induced DDX3 inhibits autophagy via miR-141 upregulation in diet-induced MASLD mice model systemMd. Musa Hossain0Amit K. Mishra1Ajay K. Yadav2Md. Ismail3Teja Naveen Sata4Amrendra K. Sah5Arnab Banik6Gopal Sharma7Senthil K. Venugopal8Faculty of Life Sciences and Biotechnology, South Asian University, New Delhi, IndiaDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, New York, USADepartment of Medical and Molecular genetics, Indiana University School of Medicine, Indianapolis, USAFaculty of Life Sciences and Biotechnology, South Asian University, New Delhi, IndiaFaculty of Life Sciences and Biotechnology, South Asian University, New Delhi, IndiaFaculty of Life Sciences and Biotechnology, South Asian University, New Delhi, IndiaFaculty of Life Sciences and Biotechnology, South Asian University, New Delhi, IndiaFaculty of Life Sciences and Biotechnology, South Asian University, New Delhi, IndiaFaculty of Life Sciences and Biotechnology, South Asian University, New Delhi, India; Corresponding author.Introduction and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the primary causes of chronic liver disease and may lead to liver cirrhosis and hepatocellular carcinoma. Recent reports suggested that DEAD-box RNA helicase (DDX3) acts as a sensor of free fat accumulation and may modulate the pathogenesis via miRNAs. Hence, we hypothesized that DDX3 might modulate MASLD progression via miRNA-141-mediated inhibition of Sirt-1 and autophagy. Materials and Methods: RNA and total protein were isolated from free fatty acid-treated HepG2 cells or CDAA-fed C57BL/6 mice (6 mice per group) for 6, 18, 32, or 54 weeks. The cells were transfected with DDX3 or miR-141 or siRNA to DDX3, and Western blots for autophagy markers were performed. Results: The FFAs induced the DDX3 and miRNA-141 expression, while downregulating Sirt-1, beclin-1, Atg7, and LC3-II. Overexpression of DDX3 resulted in increased miRNA-141. Overexpression of DDX3 or miRNA-141 downregulated Sirt-1 expression and autophagy marker proteins, while these effects were reversed with siRNA to DDX3. The expression of both DDX3 and miRNA-141 was significantly increased, while autophagy markers were downregulated in CDAA-fed mice. Conclusions: These results confirmed that FFA-induced DDX3 induced the expression of miRNA-141, which in turn targeted Sirt-1 and decreased autophagy.http://www.sciencedirect.com/science/article/pii/S1665268124005416MASLDDDX3CDAA diet fed micemiR-141Sirt-1autophagy |
| spellingShingle | Md. Musa Hossain Amit K. Mishra Ajay K. Yadav Md. Ismail Teja Naveen Sata Amrendra K. Sah Arnab Banik Gopal Sharma Senthil K. Venugopal Free fatty acid-induced DDX3 inhibits autophagy via miR-141 upregulation in diet-induced MASLD mice model system Annals of Hepatology MASLD DDX3 CDAA diet fed mice miR-141 Sirt-1 autophagy |
| title | Free fatty acid-induced DDX3 inhibits autophagy via miR-141 upregulation in diet-induced MASLD mice model system |
| title_full | Free fatty acid-induced DDX3 inhibits autophagy via miR-141 upregulation in diet-induced MASLD mice model system |
| title_fullStr | Free fatty acid-induced DDX3 inhibits autophagy via miR-141 upregulation in diet-induced MASLD mice model system |
| title_full_unstemmed | Free fatty acid-induced DDX3 inhibits autophagy via miR-141 upregulation in diet-induced MASLD mice model system |
| title_short | Free fatty acid-induced DDX3 inhibits autophagy via miR-141 upregulation in diet-induced MASLD mice model system |
| title_sort | free fatty acid induced ddx3 inhibits autophagy via mir 141 upregulation in diet induced masld mice model system |
| topic | MASLD DDX3 CDAA diet fed mice miR-141 Sirt-1 autophagy |
| url | http://www.sciencedirect.com/science/article/pii/S1665268124005416 |
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