Journal
JOURNAL OF COMPUTATIONAL BIOLOGY
Volume 26, Issue 10, Pages 1067-1079Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/cmb.2019.0021
Keywords
differentially expressed genes; drug screening; protein-protein interaction network; regulatory network; rheumatoid arthritis
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Funding
- Renji Hospital
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This study aimed to explore crucial genes that contribute to the development of rheumatoid arthritis (RA). Three GSE77298, GSE55457, and GSE55235 data sets were used to analyze the differentially expressed genes (DEGs) between RA synovial membrane tissue samples and normal synovial membrane tissue samples. Then, the functional enrichment analysis and protein-protein interactions (PPIs) construction were performed for DEGs. Subsequently, submodule analysis and regulatory network that contained transcription factors (TFs), microRNAs, and their targets were conducted. Finally, small-molecule drugs related to the DEGs were predicted. A total of 173 upregulated and 54 downregulated DEGs identified in at least 2 of 3 data sets. TYROBP, CTSS, MMP9, CXCR4, and CXCL10 were both highlighted in the PPI and submodule networks. In addition, miR-101, IRF1 TF, DUSP1, and CXCR4 had high degree in the regulatory network, and regulation pairs of miR-101-DUSP1 and IRF1 TF-CXCR4 were obtained. Drugs such as alemtuzumab and marimastat were negatively related to expression of the DEGs and might be useful drugs for RA treatment. In addition, most DEGs were involved in innate immune response (e.g., TYROBP, CCL5, CXCL10, FCGR1A, and FCGR3B) and phagosome pathway (e.g., CTSS). We suggested that miR-101 that regulated DUSP1, IRF1 TF that regulated CXCR4, as well as DEGs as TYROBP and CTSS might contribute to the RA pathogenesis. In addition, anti-inflammatory agent alemtuzumab and matrix metalloproteinase inhibitor marimastat might be useful drugs for RA treatment through functioning on their target genes.
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