Expression Profiles and Potential Functions of Long Non-Coding RNAs in the Heart of Mice With Coxsackie B3 Virus-Induced Myocarditis

Abstract

AimsLong non-coding RNAs (lncRNAs) are critical regulators of viral infection and inflammatory responses. However, the roles of lncRNAs in acute myocarditis (AM), especially fulminant myocarditis (FM), remain unclear.MethodsFM and non-fulminant myocarditis (NFM) were induced by coxsackie B3 virus (CVB3) in different mouse strains. Then, the expression profiles of the lncRNAs in the heart tissues were detected by sequencing. Finally, the patterns were analyzed by Pearson/Spearman rank correlation, Kyoto Encyclopedia of Genes and Genomes, and Cytoscape 3.7.ResultsFirst, 1,216, 983, 1,606, and 2,459 differentially expressed lncRNAs were identified in CVB3-treated A/J, C57BL/6, BALB/c, and C3H mice with myocarditis, respectively. Among them, 88 lncRNAs were commonly dysregulated in all four models. Quantitative real-time polymerase chain reaction analyses further confirmed that four out of the top six commonly dysregulated lncRNAs were upregulated in all four models. Moreover, the levels of ENSMUST00000188819, ENSMUST00000199139, and ENSMUST00000222401 were significantly elevated in the heart and spleen and correlated with the severity of cardiac inflammatory infiltration. Meanwhile, 923 FM-specific dysregulated lncRNAs were detected, among which the levels of MSTRG.26098.49, MSTRG.31307.11, MSTRG.31357.2, and MSTRG.32881.28 were highly correlated with LVEF.ConclusionExpression of lncRNAs is significantly dysregulated in acute myocarditis, which may play different roles in the progression of AM.

Analysis of long noncoding RNAs and messenger RNAs expression profiles in the hearts of mice with acute viral myocarditis

“…Results showed that the target genes were mainly involved in metabolic and immune‐related processes, which was highly consistent with the enrichment analysis results of identified DEmRNAs, indicating that DElncRNAs may participate in the progression of AVMC by interacting with DEmRNAs in this study. Our findings nicely complement and extend the experimental work of Nie et al 38 Then, to further study the complicated regulatory relationship between DElncRNAs and their co‐expressed DEmRNAs, we selected three important pathways (cytokine‐cytokine receptor interaction, MAPK signaling pathway, and PI3K‐Akt signaling pathway) and conducted interaction networks using the Cytoscape software. In the networks, numerous connections between DElncRNAs and DEmRNAs suggest the complexity of the molecular mechanisms of AVMC.…”

“…Recently, Nie et al 38 investigated the altered expression of lncRNAs in the hearts of mice with fulminant myocarditis and non‐fulminant myocarditis and focused on the roles of cis‐targets through the KEGG pathway enrichment analysis. In general, lncRNAs contribute to gene expression regulation at different levels by cis or trans‐acting 31 .…”

Identification of Cardiac CircRNAs in Mice With CVB3-Induced Myocarditis

“…MiRNAs targets of circRNAs were predicted by miRnada and psRobot. Cytargetlinker was used in Cytoscape for the miRNA-mRNA network as described previously (Nie et al, 2021).…”