MicroRNA-disease Network Analysis Repurposes Methotrexate for the Treatment of Abdominal Aortic Aneurysm in Mice

Yicong Shen; Yuanxu Gao; Jiangcheng Shi; Zhou Huang; Rongbo Dai; Yi Fu; Yuan Zhou; Wei Kong; Qinghua Cui

doi:10.1016/j.gpb.2022.08.002

MicroRNA-disease Network Analysis Repurposes Methotrexate for the Treatment of Abdominal Aortic Aneurysm in Mice

Genomics Proteomics Bioinformatics. 2023 Oct;21(5):1030-1042. doi: 10.1016/j.gpb.2022.08.002. Epub 2022 Aug 24.

Authors

Yicong Shen¹, Yuanxu Gao², Jiangcheng Shi³, Zhou Huang³, Rongbo Dai¹, Yi Fu¹, Yuan Zhou³, Wei Kong⁴, Qinghua Cui⁵

Affiliations

¹ Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China.
² Department 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, China.
³ 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.
⁴ Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China. Electronic address: kongw@bjmu.edu.cn.
⁵ 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. Electronic address: cuiqinghua@bjmu.edu.cn.

Abstract

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.

Keywords: Abdominal aortic aneurysm; Autoimmune disease; Methotrexate; MicroRNA-derived disease network; Network medicine.

MeSH terms

Animals
Aorta, Abdominal
Aortic Aneurysm, Abdominal* / drug therapy
Aortic Aneurysm, Abdominal* / genetics
Autoimmune Diseases*
Disease Models, Animal
Methotrexate / therapeutic use
Mice
MicroRNAs* / genetics

Substances

MicroRNAs
Methotrexate