Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Cell-Based Therapies Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Comb Chem High Throughput Screen. 2021;24(2):195-212. doi: 10.2174/1386207323666200605150024.
Considering the molecular complexity and heterogeneity of rheumatoid arthritis (RA), the identification of novel molecular contributors involved in RA initiation and progression using systems biology approaches will open up potential therapeutic strategies. The bioinformatics method allows the detection of associated miRNA-mRNA as both therapeutic and prognostic targets for RA.
This research used a system biology approach based on a systematic re-analysis of the RA-related microarray datasets in the NCBI Gene Expression Omnibus (GEO) database to find out deregulated miRNAs. We then studied the deregulated miRNA-mRNA using Enrichr and Molecular Signatures Database (MSigDB) to identify novel RA-related markers followed by an overview of miRNA-mRNA interaction networks and RA-related pathways.
This research mainly focused on mRNA and miRNA interactions in all tissues and blood/serum associated with RA to obtain a comprehensive knowledge of RA. Recent systems biology approach analyzed seven independent studies and presented important RA-related deregulated miRNAs (miR-145-5p, miR-146a-5p, miR-155-5p, miR-15a-5p, miR-29c-3p, miR- 103a-3p, miR-125a-5p, miR-125b-5p, miR-218); upregulation of miR-125b is shown in the study (GSE71600). While the findings of the Enrichr showed cytokine and vitamin D receptor pathways and inflammatory pathways. Further analysis revealed a negative correlation between the vitamin D receptor (VDR) and miR-125b in RA-associated gene expression.
Since vitamin D is capable of regulating the immune homeostasis and decreasing the autoimmune process through its receptor (VDR), it is regarded as a potential target for RA. According to the results obtained, a comparative correlation between negative expression of the vitamin D receptor (VDR) and miR-125b was suggested in RA. The increasing miR-125b expression would reduce the VitD uptake through its receptor.
鉴于类风湿关节炎 (RA) 的分子复杂性和异质性，使用系统生物学方法识别参与 RA 起始和进展的新分子贡献物将开辟潜在的治疗策略。生物信息学方法允许检测相关的 miRNA-mRNA，作为 RA 的治疗和预后靶点。
本研究使用基于系统生物学的方法，对 NCBI 基因表达综合数据库 (GEO) 中与 RA 相关的微阵列数据集进行系统重新分析，以找出失调的 miRNA。然后，我们使用 Enrichr 和分子特征数据库 (MSigDB) 研究失调的 miRNA-mRNA，以识别新的 RA 相关标志物，然后概述 miRNA-mRNA 相互作用网络和 RA 相关途径。
本研究主要集中在与 RA 相关的所有组织和血液/血清中的 mRNA 和 miRNA 相互作用，以获得对 RA 的全面了解。最近的系统生物学方法分析了 7 项独立研究，并提出了重要的 RA 相关失调 miRNA（miR-145-5p、miR-146a-5p、miR-155-5p、miR-15a-5p、miR-29c-3p、miR-103a-3p、miR-125a-5p、miR-125b-5p、miR-218）；研究（GSE71600）显示 miR-125b 的上调。而 Enrichr 的发现显示了细胞因子和维生素 D 受体途径以及炎症途径。进一步分析表明，维生素 D 受体 (VDR) 与 RA 相关基因表达中的 miR-125b 呈负相关。
由于维生素 D 能够通过其受体 (VDR) 调节免疫稳态并减少自身免疫过程，因此它被视为 RA 的潜在靶点。根据所获得的结果，建议在 RA 中存在维生素 D 受体 (VDR) 负表达与 miR-125b 之间的比较相关性。miR-125b 表达的增加会通过其受体减少 VitD 的摄取。
