Identification of Potential ceRNA Network and Patterns of Immune Cell Infiltration in Systemic Sclerosis-Associated Interstitial Lung Disease.

PURPOSE:Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is one of the most severe complications of systemic sclerosis (SSc) and is the leading cause of SSc-related deaths. However, the precise pathogenesis of pulmonary fibrosis in SSc-ILD remains unknown. This study aimed to evaluate the competing endogenous RNA (ceRNA) regulatory network and immune cell infiltration patterns in SSc-ILD. METHODS:One microRNA (miRNA) and three messenger RNA (mRNA) microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. Then, the differentially expressed miRNAs (DEmiRs) and mRNAs (DEMs) between SSc-ILD patients and normal controls were identified, respectively, followed by the prediction of the target genes and target lncRNAs of DEmiRs. The overlapping genes between DEmiRs target genes and DEMs were identified as core mRNAs to construct the ceRNA network. In addition, the "Cell Type Identification by Estimating Relative Subsets of Known RNA Transcripts (CIBERSORT)" algorithm was used to analyze the composition of infiltrating immune cells in lung tissues of SSc-ILD patients and controls, and differentially expressed immune cells were recognized. The correlation between immune cells and core mRNAs was evaluated by Pearson correlation analysis. RESULTS:Totally, 42 SSc-ILD lung tissues and 18 normal lung tissues were included in this study. We identified 35 DEmiRs and 142 DEMs and predicted 1,265 target genes of DEmiRs. Then, 9 core mRNAs related to SSc-ILD were recognized, which were the overlapping genes between DEmiRs target genes and DEMs. Meanwhile, 9 DEmiRs related to core mRNAs were identified reversely, and their target lncRNAs were predicted. In total, 9 DEmiRs, 9 core mRNAs, and 51 predicted lncRNAs were integrated to construct the ceRNA regulatory network of SSc-ILD. In addition, 9 types of immune cells were differentially expressed in lung tissues between SSc-ILD patients and controls. Some core mRNAs, such as COL1A1, FOS, and EDN1, were positively or negatively correlated with the number of infiltrating immune cells. CONCLUSION:This is the first comprehensive study to construct the potential ceRNA regulatory network and analyze the composition of infiltrating immune cells in lung tissues of SSc-ILD patients, which improves our understanding of the pathogenesis of SSc-ILD.