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Journal of Computational Biology : a... Oct 2019This 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...
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. , , , , and were both highlighted in the PPI and submodule networks. In addition, miR-101, TF, , and had high degree in the regulatory network, and regulation pairs of miR-101- and TF- 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., , , , , and ) and phagosome pathway (e.g., ). We suggested that miR-101 that regulated , TF that regulated , as well as as and 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.
Topics: Arthritis, Rheumatoid; Cartilage; Dual Specificity Phosphatase 1; Gene Expression Profiling; Gene Ontology; Gene Regulatory Networks; Humans; MicroRNAs; Protein Interaction Maps; Synovial Membrane; Transcriptome; Up-Regulation
PubMed: 31246497
DOI: 10.1089/cmb.2019.0021