背景:类风湿性关节炎(RA)和骨质疏松症(OP)被认为是复杂的疾病。在最近的研究中,据报道,RA和OP之间的正相关引发了越来越多的研究兴趣.本研究旨在探讨与RA和OP的关键基因相关的药物,使用生物信息学方法,对药物的再利用。
方法:鉴定RA和OP基因。使用STRING和Cytoscape构建和分析了RA-OPPPI网络,分别。提取并丰富了Hub基因和模块,通过WebGestalt和g:Profiler。使用DGIDB鉴定与关键基因相关的药物,并使用miRWalk和miRNet提取miRNAs。
结果:通过网络集群,获得了在免疫系统中具有重要作用的五个重要模块。IL6,TNF,IL1B,STAT3,TGFB1,TP53,HIF1A,CCL2、IL10和MMP9被发现是RA-OP网络中的前10个hub基因。Hub基因被证明对炎症反应有影响,细胞因子受体结合的重要功能,大多位于细胞外空间。通过调查与hub基因相关的药物,16种药物被确定为再利用的候选药物。这10种药物包括羟氯喹,英夫利昔单抗,阿达木单抗,Etanercept,Certolizumab,环孢菌素,Diacein,Gevokizumab,Canakinumab,和Olokizumab建议用于OP。此外,包括吡非尼酮在内的六种药物,己酮可可碱,瓦迪梅赞,Rilonacept,Metelimumab,和西妥昔单抗在炎症控制中具有重要作用,被提议用于RA和OP。
结论:本研究结果可为RA和OP的发病机制和治疗提供新的见解。
BACKGROUND: Rheumatoid arthritis (RA) and osteoporosis (OP) are considered to be complex diseases. In recent studies, a positive association between RA and OP has been reported triggering growing research interest. This study aims to investigate the drugs related to critical genes in RA and OP, using bioinformatics approaches, toward drug repurposing.
METHODS: RA and OP genes were identified. The RA-OP PPI network was constructed and analyzed using the STRING and Cytoscape, respectively. Hub genes and modules were extracted and enriched Gene Ontology, through the WebGestalt and g:Profiler. The identification of the drugs related to critical genes using the DGIDB, and extracted the miRNAs using miRWalk and miRNet.
RESULTS: By network clustering, five significant modules were obtained that have important roles in the immune system. IL6, TNF, IL1B, STAT3, TGFB1, TP53, HIF1A, CCL2, IL10, and MMP9 were found as the top 10 hub genes in the RA-OP network. Hub genes were shown to have implications in inflammatory response, significant functions in cytokine receptor binding, and localized mostly in extracellular space. By investigating the drugs related to hub genes, 16 drugs were identified as repurposing candidate drugs. The 10 drugs included Hydroxychloroquine, Infliximab, Adalimumab, Etanercept, Certolizumab, Cyclosporine, Diacerein, Gevokizumab, Canakinumab, and Olokizumab proposed for OP. Also, six drugs including Pirfenidone, Pentoxifylline, Vadimezan, Rilonacept, Metelimumab, and Siltuximab have important roles in inflammatory control and were proposed for both RA and OP.
CONCLUSIONS: The results of the present study can provide novel insights into the pathogenesis and treatment of RA and OP.