首页|MicroRNA-disease Network Analysis Repurposes Methotrexate for the Treatment of Abdominal Aortic Aneurysm in Mice
MicroRNA-disease Network Analysis Repurposes Methotrexate for the Treatment of Abdominal Aortic Aneurysm in Mice
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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 algo-rithm 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.
Yicong Shen、Yuanxu Gao、Jiangcheng Shi、Zhou Huang、Rongbo Dai、Yi Fu、Yuan Zhou、Wei Kong、Qinghua Cui
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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
PKU-Baidu FundNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of China
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