Identification of mitochondrial function‐associated lncRNAs in septic mice myocardium

Abstract

The present study aimed to analyze long noncoding RNA (lncRNA) and messenger RNA (mRNA) expression profiles in septic mice heart and to identify potential lncRNAs and mRNAs that be responsible for cardiac mitochondrial dysfunction during sepsis. Mice were treated with 10 mg/kg of lipopolysaccharides to induce sepsis. LncRNAs and mRNAs expression were evaluated by using lncRNA and mRNA microarray or real‐time polymerase chain reaction technique. LncRNA‐mRNA coexpression network assay, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed. The results showed that 1275 lncRNAs were differentially expressed in septic myocardium compared with those in the control group. A total of 2769 mRNAs were dysregulated in septic mice heart, most of which are mainly related to the process of inflammation, mitochondrial metabolism, oxidative stress, and apoptosis. Coexpression network analysis showed that 14 lncRNAs were highly correlated with 11 mitochondria‐related differentially expressed mRNA. Among all lncRNAs and their cis‐acting mRNAs, 41 lncRNAs‐mRNA pairs (such as NONMMUG004378 and Apaf1 gene) were enriched in GO terms and KEGG pathways. In summary, we gained some specific lncRNAs and their potential target mRNAs that might be involved in mitochondrial dysfunction in septic myocardium. These findings provide a panoramic view of lncRNA and might allow developing new treatment strategies for sepsis.

The Role of Long Non-coding RNAs in Sepsis-Induced Cardiac Dysfunction

“…Additionally, 28 upregulated and 61 downregulated lncRNAs were identified in the public reported NCBI GEO dataset ( 22 ). Similar analyses based on cardiac tissue from mouse or rat sepsis models reported 74 ( 23 ) to 1,275 DElncRNAs, and revealed 14 lncRNAs that were highly correlated with 11 mitochondria-related differentially expressed mRNAs ( 24 ) and 11 differentially expressed circRNAs ( 25 ). Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that upregulated lncRNAs were significantly enriched in the p53, NF-κB, and HIF-1 signaling pathways ( 26 ).…”

“…As previously discussed, numerous lncRNAs are aberrantly expressed in SICD compared with normal cardiac tissue or cell lines, and this is useful to distinguish SICD patients from healthy cohorts. Although nearly all lncRNAs with direct evidence of their involvement in SICD were declared as potential biomarkers of SICD, those lncRNAs also show aberrant expression patterns in sepsis without cardiac dysfunction, especially critical patients, and in other non-sepsis situations such as MI, I/R, and acute kidney injury ( 21 , 22 , 24 , 26 , 110 , 114 , 148 ). This reduces the reliability of using these lncRNAs as potential biomarkers of SICD.…”

Cuproptosis-associated lncRNAs discern prognosis and immune microenvironment in sarcoma victims

“…Total RNA was purified from FFPE samples and only samples with DV200 ≥ 30% were selected for subsequent RNA sequence analysis. See our previous report for more details on the method (Shi et al, 2021).…”

Novel Insights Into the Potential Mechanisms of N6-Methyladenosine RNA Modification on Sepsis-Induced Cardiovascular Dysfunction: An Update Summary on Direct and Indirect Evidences

“…The heart is rich in mitochondria, which are involved in both energy provision and intracellular calcium regulation; consequently, the degree of mitochondrial dysfunction is tightly linked to SICD and the prognosis of this condition ( Lin et al, 2020a ; Shi et al, 2021a ; Wang et al, 2021a ). The activities of complexes I and II of the mitochondrial respiratory chain were diminished in the hearts from animals with sepsis ( Piel et al, 2007 ; Neviere et al, 2016 ), and this might be due to the detrimental effects of sepsis mediators such as NO, TNF-α, IL-1β, etc.…”