Faculty of Mathematics and Computer Science, Department of Bioinformatics, Bahonar University, Kerman, Iran; Bahonar Bioinformatics Lab (BBL), Iran.
Department of Oncology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Comput Biol Med. 2024 Sep;180:108912. doi: 10.1016/j.compbiomed.2024.108912. Epub 2024 Jul 29.
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.
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.
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.
The results of the present study can provide novel insights into the pathogenesis and treatment of RA and OP.
类风湿关节炎（RA）和骨质疏松症（OP）被认为是复杂的疾病。最近的研究报告称，RA 和 OP 之间存在正相关关系，这引发了越来越多的研究兴趣。本研究旨在使用生物信息学方法研究与 RA 和 OP 相关的关键基因的药物，以进行药物再利用。
确定 RA 和 OP 基因。使用 STRING 和 Cytoscape 分别构建和分析 RA-OP PPI 网络。通过 WebGestalt 和 g：Profiler，提取和富集基因本体论中的枢纽基因和模块。使用 DGIDB 识别与关键基因相关的药物，并使用 miRWalk 和 miRNet 提取 miRNA。
通过网络聚类，获得了五个重要的模块，它们在免疫系统中具有重要作用。IL6、TNF、IL1B、STAT3、TGFB1、TP53、HIF1A、CCL2、IL10 和 MMP9 被确定为 RA-OP 网络中的前 10 个枢纽基因。枢纽基因在炎症反应中具有重要意义，在细胞因子受体结合方面具有显著功能，并且主要位于细胞外空间。通过研究与枢纽基因相关的药物，确定了 16 种药物作为再利用候选药物。其中包括羟氯喹、英夫利昔单抗、阿达木单抗、依那西普、certolizumab、环孢素、二乙酰氨己酸、gevokizumab、卡那单抗和 olokizumab，这些药物被提议用于 OP。此外，还包括 pirfenidone、pentoxifylline、vadimezan、rilonacept、metelimumab 和 siltuximab 等六种药物，它们在炎症控制方面具有重要作用，被提议用于 RA 和 OP。
本研究的结果可为 RA 和 OP 的发病机制和治疗提供新的见解。
