Abstract
BACKGROUND: Long noncoding RNAs (lncRNAs) play important roles in the regulation of immunological and apoptotic function. This study aimed to explore the critical immune- and apoptosis-related lncRNAs in the occurrence and development of Henoch-Schönlein purpura nephritis (HSPN) in children. METHODS: Differential analysis was employed to identify the differentially expressed lncRNAs, as well as the immune- and apoptosis-related mRNAs in children with HSPN. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to validate the immunological and apoptotic roles of the differentially expressed immune- and apoptosis-related lncRNAs and mRNAs. Spearman's correlation analysis was performed to analyze the differentially expressed lncRNAs and immune- and apoptosis-related messenger RNAs (mRNAs). Based on the competing endogenous RNA (ceRNA) mechanism, the immune- and apoptosis-related lncRNA-microRNA (miRNA)-mRNA regulatory network was then constructed in children with HSPN. The expression levels of the lncRNAs in the lncRNA-miRNA-mRNA regulatory network were further confirmed by quantitative real-time polymerase chain in the peripheral blood samples of children with HSPN. RESULTS: By intersecting the differentially expressed immune-related and apoptosis-related genes through GO and KEGG analyses, a total of 43 genes were identified in children with HSPN, and 100 lncRNAs highly correlated with the above genes were identified by correlation analysis. The immune- and apoptosis-related lncRNA-miRNA-mRNA regulatory network was then established based on ceRNA mechanism. Dysregulation of a total of 11 lncRNAs were discovered, including upregulated SNHG3, LINC00152, TUG1, GAS5, FGD5-AS1, DLEU2, and SCARNA9; and downregulated SNHG1, NEAT1, DISC1-IT1, and PVT1. The validation conducted in the clinical samples also suggested that the above lncRNAs in the specific regulatory network may act as potential biomarkers with prognosis in children with HSPN. CONCLUSIONS: LncRNAs may play essential regulatory roles in the occurrence and development of HSPN in children, and the immune- and apoptosis-related lncRNA-miRNA-mRNA regulatory network might be the underlying molecular mechanism that dissects the disease pathogenesis. In addition, the dysregulated lncRNAs in the regulatory network may be novel biomarkers for the diagnosis and therapy of HSPN in children.