Identification of lncRNA–miRNA–mRNA networks in circulating exosomes as potential biomarkers for systemic sclerosis

作者：Xiaolin Sun, Tiantian Ding, Baoyue Wang, Zhifang Chang, Hongchang Fei, Lixia Geng, Yongfu Wang · 发表于：Frontiers in Medicine · 年份：2023 · DOI：10.3389/fmed.2023.1111812 · 被引用次数：12 · 研究领域：Systemic Sclerosis and Related Diseases、Cancer-related molecular mechanisms research、Diagnosis and Treatment of Venous Diseases

Objective This study aimed to analyze potential biomarkers for systemic sclerosis (SSc) by constructing lncRNA–miRNA–mRNA networks in circulating exosomes (cirexos). Materials and methods Differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) in SSc cirexos were screened using high-throughput sequencing and detected with real-time quantitative PCR (RT-qPCR). Differentially expressed genes (DEGs) were analyzed using the DisGeNET, GeneCards, GSEA4.2.3, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Receiver operating characteristic (ROC) curves, correlation analyses, and a double-luciferase reporter gene detection assay were used to analyze competing endogenous RNA (ceRNA) networks and clinical data. Results In this study, 286 DEmRNAs and 192 DElncRNAs were screened, of which 18 DEGs were the same as the SSc-related genes. The main SSc-related pathways included extracellular matrix (ECM) receptor interaction, local adhesion, platelet activation, and IgA production by the intestinal immune network. A hub gene, COL1A1 , was obtained by a protein–protein interaction (PPI) network. Four ceRNA networks were predicted through Cytoscape. The relative expression levels of COL1A1 , ENST0000313807, and NON-HSAT194388.1 were significantly higher in SSc, while the relative expression levels of hsa-miR-29a-3p, hsa-miR-29b-3p, and hsa-miR-29c-3p were significantly lower in SSc ( P < 0.05). The ROC curve showed that the ENST00000313807-hsa-m...