HMGCS2 and AMACR as potential targets linking mitochondrial dysfunction and ulcerative colitis
Abstract Ulcerative colitis (UC) is characterised notably by an imbalance in intestinal mucosal homeostasis. Although mitochondrial dysfunction has been identified as a potential contributor to this imbalance, it remains an incomplete understanding. Consequently, further investigation into the role...
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Nature Portfolio
2024-12-01
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| Online Access: | https://doi.org/10.1038/s41598-024-82900-y |
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| author | Rui Zhu Xinyu Bai Zhangqin Li Hao Liang Huixian Song Lifang Chen Yinglei Miao Fengrui Zhang Junkun Niu |
| author_facet | Rui Zhu Xinyu Bai Zhangqin Li Hao Liang Huixian Song Lifang Chen Yinglei Miao Fengrui Zhang Junkun Niu |
| author_sort | Rui Zhu |
| collection | DOAJ |
| description | Abstract Ulcerative colitis (UC) is characterised notably by an imbalance in intestinal mucosal homeostasis. Although mitochondrial dysfunction has been identified as a potential contributor to this imbalance, it remains an incomplete understanding. Consequently, further investigation into the role of mitochondria in UC is warranted. The study focusing on the GSE87466 dataset for differential gene expression analysis. Mitochondria-related genes were sourced from the MitoCart3.0 database. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to identify hub genes. The intersection of DEGs, hub genes, and mitochondria-related genes facilitated the identification of 14 mitochondria-related differentially expressed genes (MitoDEGs). Three machine learning algorithms were then applied to select signature MitoDEGs specific to UC: HMGCS2 and AMACR. They have decreased expression in UC patients and have a high diagnostic value for UC. In the inflammatory environment, knockout of both HMGCS2 and AMACR showed disruption of mitochondrial structure and function. Among them, the AMACR knockdown group had an increased number of damaged mitochondria and a significant reduction in the length, area and circumference of MAMs. Therefore, the study identified two new signature MitoDEGs in UC. HMGCS2 and AMACR provide insights into the interplay between mitochondrial dysfunction and UC intestinal mucosal homeostasis. |
| format | Article |
| id | doaj-art-943dd804918148f381bca7ca45bb7678 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-943dd804918148f381bca7ca45bb76782025-01-05T12:28:59ZengNature PortfolioScientific Reports2045-23222024-12-0114111510.1038/s41598-024-82900-yHMGCS2 and AMACR as potential targets linking mitochondrial dysfunction and ulcerative colitisRui Zhu0Xinyu Bai1Zhangqin Li2Hao Liang3Huixian Song4Lifang Chen5Yinglei Miao6Fengrui Zhang7Junkun Niu8Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical UniversityDepartment of Gastroenterology, The First Affiliated Hospital of Kunming Medical UniversityDepartment of Gastroenterology, The First Affiliated Hospital of Kunming Medical UniversityDepartment of Gastroenterology, The First Affiliated Hospital of Kunming Medical UniversityDepartment of Gastroenterology, The First Affiliated Hospital of Kunming Medical UniversityXishuangbanna Dai Autonomous Prefecture People’s HospitalDepartment of Gastroenterology, The First Affiliated Hospital of Kunming Medical UniversityDepartment of Gastroenterology, The First Affiliated Hospital of Kunming Medical UniversityDepartment of Gastroenterology, The First Affiliated Hospital of Kunming Medical UniversityAbstract Ulcerative colitis (UC) is characterised notably by an imbalance in intestinal mucosal homeostasis. Although mitochondrial dysfunction has been identified as a potential contributor to this imbalance, it remains an incomplete understanding. Consequently, further investigation into the role of mitochondria in UC is warranted. The study focusing on the GSE87466 dataset for differential gene expression analysis. Mitochondria-related genes were sourced from the MitoCart3.0 database. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to identify hub genes. The intersection of DEGs, hub genes, and mitochondria-related genes facilitated the identification of 14 mitochondria-related differentially expressed genes (MitoDEGs). Three machine learning algorithms were then applied to select signature MitoDEGs specific to UC: HMGCS2 and AMACR. They have decreased expression in UC patients and have a high diagnostic value for UC. In the inflammatory environment, knockout of both HMGCS2 and AMACR showed disruption of mitochondrial structure and function. Among them, the AMACR knockdown group had an increased number of damaged mitochondria and a significant reduction in the length, area and circumference of MAMs. Therefore, the study identified two new signature MitoDEGs in UC. HMGCS2 and AMACR provide insights into the interplay between mitochondrial dysfunction and UC intestinal mucosal homeostasis.https://doi.org/10.1038/s41598-024-82900-yUlcerative colitisMitochondriaWGCNAMachine learningImmune infiltration |
| spellingShingle | Rui Zhu Xinyu Bai Zhangqin Li Hao Liang Huixian Song Lifang Chen Yinglei Miao Fengrui Zhang Junkun Niu HMGCS2 and AMACR as potential targets linking mitochondrial dysfunction and ulcerative colitis Scientific Reports Ulcerative colitis Mitochondria WGCNA Machine learning Immune infiltration |
| title | HMGCS2 and AMACR as potential targets linking mitochondrial dysfunction and ulcerative colitis |
| title_full | HMGCS2 and AMACR as potential targets linking mitochondrial dysfunction and ulcerative colitis |
| title_fullStr | HMGCS2 and AMACR as potential targets linking mitochondrial dysfunction and ulcerative colitis |
| title_full_unstemmed | HMGCS2 and AMACR as potential targets linking mitochondrial dysfunction and ulcerative colitis |
| title_short | HMGCS2 and AMACR as potential targets linking mitochondrial dysfunction and ulcerative colitis |
| title_sort | hmgcs2 and amacr as potential targets linking mitochondrial dysfunction and ulcerative colitis |
| topic | Ulcerative colitis Mitochondria WGCNA Machine learning Immune infiltration |
| url | https://doi.org/10.1038/s41598-024-82900-y |
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