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Identification of mitochondria metabolism-related biomarkers associated with the development of rheumatoid arthritis
Ruiyang Xu1, Zhixuan Zhang1, Min Zhou2
1Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, China.
Abstract:
Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disorder that has serious physical and mental health implications. It is evident that disruptions to mitochondrial function have a considerable impact on the survival, activation, and differentiation of RA-associated immune and nonimmune cells. However, the mechanisms of mitochondria metabolism in RA remain unclear. This study identified mitochondrial metabolism-related genes that may contribute to the pathogenesis of RA. The following data were sourced from public databases: transcriptome data of RA and mitochondrial metabolism-related genes. The protein-protein interaction network, machine learning, and gene expression analyses were used to screen the biomarkers. A nomogram was developed to assess the risk of RA. The validity of this nomogram was then tested through the calibration curve and the receiver operating characteristic curve. The biological characteristics and immune infiltration landscape of the biomarkers and RA were then evaluated using functional enrichment and immune infiltration analyses. Ultimately, a molecular regulatory pathway of the biomarkers was constructed. COX7B, NDUFB3, and UQCRQ were identified as the biomarkers. Notably, the ribosome and oxidative phosphorylation were the pathway co-enriched by these 3 biomarkers. The 8 immune cell types showed notable distinctions between RA and control groups. Among them, COX7B, NDUFB3, and UQCRQ were all significantly shown to have an inverse relationship with regulatory T cells (cor < -0.40, P < .001). Finally, long noncoding RNA (lncRNA, NEAT1) exerted a regulatory influence on COX7B, NDUFB3, and UQCRQ by regulating hsa-miR-514a-3p, hsa-miR-379-5p, and hsa-miR-144-3p, respectively. This study identified and validated 3 biomarkers (COX7B, NDUFB3, and UQCRQ) associated with RA, which proved a foundation for further research into the relationship between mitochondria metabolism and RA.
