MicroRNA–disease Network Analysis Repurposes Methotrexate for the Treatment of Abdominal Aortic Aneurysm in Mice
Abdominal aortic aneurysm (AAA) is a permanent dilatation of the abdominal aorta and is highly lethal. The main purpose of the current study is to search for noninvasive medical therapies for AAA, for which there is currently no effective drug therapy. Network medicine represents a cutting-edge tech...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-10-01
|
| Series: | Genomics, Proteomics & Bioinformatics |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S167202292200095X |
| _version_ | 1797281188258250752 |
|---|---|
| author | Yicong Shen Yuanxu Gao Jiangcheng Shi Zhou Huang Rongbo Dai Yi Fu Yuan Zhou Wei Kong Qinghua Cui |
| author_facet | Yicong Shen Yuanxu Gao Jiangcheng Shi Zhou Huang Rongbo Dai Yi Fu Yuan Zhou Wei Kong Qinghua Cui |
| author_sort | Yicong Shen |
| collection | DOAJ |
| description | Abdominal aortic aneurysm (AAA) is a permanent dilatation of the abdominal aorta and is highly lethal. The main purpose of the current study is to search for noninvasive medical therapies for AAA, for which there is currently no effective drug therapy. Network medicine represents a cutting-edge technology, as analysis and modeling of disease networks can provide critical clues regarding the etiology of specific diseases and therapeutics that may be effective. Here, we proposed a novel algorithm to quantify disease relations based on a large accumulated microRNA–disease association dataset and then built a disease network covering 15 disease classes and 304 diseases. Analysis revealed some patterns for these diseases. For instance, diseases tended to be clustered and coherent in the network. Surprisingly, we found that AAA showed the strongest similarity with rheumatoid arthritis and systemic lupus erythematosus, both of which are autoimmune diseases, suggesting that AAA could be one type of autoimmune diseases in etiology. Based on this observation, we further hypothesized that drugs for autoimmune diseases could be repurposed for the prevention and therapy of AAA. Finally, animal experiments confirmed that methotrexate, a drug for autoimmune diseases, was able to alleviate the formation and development of AAA. |
| first_indexed | 2024-03-07T16:53:52Z |
| format | Article |
| id | doaj.art-5aa36840e3d94a8c8879c51c2e1d0087 |
| institution | Directory Open Access Journal |
| issn | 1672-0229 |
| language | English |
| last_indexed | 2024-03-07T16:53:52Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Genomics, Proteomics & Bioinformatics |
| spelling | doaj.art-5aa36840e3d94a8c8879c51c2e1d00872024-03-03T04:29:18ZengElsevierGenomics, Proteomics & Bioinformatics1672-02292023-10-0121510301042MicroRNA–disease Network Analysis Repurposes Methotrexate for the Treatment of Abdominal Aortic Aneurysm in MiceYicong Shen0Yuanxu Gao1Jiangcheng Shi2Zhou Huang3Rongbo Dai4Yi Fu5Yuan Zhou6Wei Kong7Qinghua Cui8Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, ChinaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China; State Key Laboratory of Lunar and Planetary Sciences, Macau University of Science and Technology, Macao Special Administrative Region 999078, China; Department of Biomedical Informatics, Center for Noncoding RNA Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China; Department of Biomedical Informatics, Center for Noncoding RNA Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China; Department of Biomedical Informatics, Center for Noncoding RNA Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, ChinaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, ChinaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China; Department of Biomedical Informatics, Center for Noncoding RNA Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China; Corresponding authors.Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China; Department of Biomedical Informatics, Center for Noncoding RNA Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China; Corresponding authors.Abdominal aortic aneurysm (AAA) is a permanent dilatation of the abdominal aorta and is highly lethal. The main purpose of the current study is to search for noninvasive medical therapies for AAA, for which there is currently no effective drug therapy. Network medicine represents a cutting-edge technology, as analysis and modeling of disease networks can provide critical clues regarding the etiology of specific diseases and therapeutics that may be effective. Here, we proposed a novel algorithm to quantify disease relations based on a large accumulated microRNA–disease association dataset and then built a disease network covering 15 disease classes and 304 diseases. Analysis revealed some patterns for these diseases. For instance, diseases tended to be clustered and coherent in the network. Surprisingly, we found that AAA showed the strongest similarity with rheumatoid arthritis and systemic lupus erythematosus, both of which are autoimmune diseases, suggesting that AAA could be one type of autoimmune diseases in etiology. Based on this observation, we further hypothesized that drugs for autoimmune diseases could be repurposed for the prevention and therapy of AAA. Finally, animal experiments confirmed that methotrexate, a drug for autoimmune diseases, was able to alleviate the formation and development of AAA.http://www.sciencedirect.com/science/article/pii/S167202292200095XAbdominal aortic aneurysmNetwork medicineMicroRNA-derived disease networkAutoimmune diseaseMethotrexate |
| spellingShingle | Yicong Shen Yuanxu Gao Jiangcheng Shi Zhou Huang Rongbo Dai Yi Fu Yuan Zhou Wei Kong Qinghua Cui MicroRNA–disease Network Analysis Repurposes Methotrexate for the Treatment of Abdominal Aortic Aneurysm in Mice Genomics, Proteomics & Bioinformatics Abdominal aortic aneurysm Network medicine MicroRNA-derived disease network Autoimmune disease Methotrexate |
| title | MicroRNA–disease Network Analysis Repurposes Methotrexate for the Treatment of Abdominal Aortic Aneurysm in Mice |
| title_full | MicroRNA–disease Network Analysis Repurposes Methotrexate for the Treatment of Abdominal Aortic Aneurysm in Mice |
| title_fullStr | MicroRNA–disease Network Analysis Repurposes Methotrexate for the Treatment of Abdominal Aortic Aneurysm in Mice |
| title_full_unstemmed | MicroRNA–disease Network Analysis Repurposes Methotrexate for the Treatment of Abdominal Aortic Aneurysm in Mice |
| title_short | MicroRNA–disease Network Analysis Repurposes Methotrexate for the Treatment of Abdominal Aortic Aneurysm in Mice |
| title_sort | microrna disease network analysis repurposes methotrexate for the treatment of abdominal aortic aneurysm in mice |
| topic | Abdominal aortic aneurysm Network medicine MicroRNA-derived disease network Autoimmune disease Methotrexate |
| url | http://www.sciencedirect.com/science/article/pii/S167202292200095X |
| work_keys_str_mv | AT yicongshen micrornadiseasenetworkanalysisrepurposesmethotrexateforthetreatmentofabdominalaorticaneurysminmice AT yuanxugao micrornadiseasenetworkanalysisrepurposesmethotrexateforthetreatmentofabdominalaorticaneurysminmice AT jiangchengshi micrornadiseasenetworkanalysisrepurposesmethotrexateforthetreatmentofabdominalaorticaneurysminmice AT zhouhuang micrornadiseasenetworkanalysisrepurposesmethotrexateforthetreatmentofabdominalaorticaneurysminmice AT rongbodai micrornadiseasenetworkanalysisrepurposesmethotrexateforthetreatmentofabdominalaorticaneurysminmice AT yifu micrornadiseasenetworkanalysisrepurposesmethotrexateforthetreatmentofabdominalaorticaneurysminmice AT yuanzhou micrornadiseasenetworkanalysisrepurposesmethotrexateforthetreatmentofabdominalaorticaneurysminmice AT weikong micrornadiseasenetworkanalysisrepurposesmethotrexateforthetreatmentofabdominalaorticaneurysminmice AT qinghuacui micrornadiseasenetworkanalysisrepurposesmethotrexateforthetreatmentofabdominalaorticaneurysminmice |