Profiles of differentially expressed long noncoding RNAs and messenger RNAs in the myocardium of septic mice

Chengbao Li; Yongchao Liu; Jing Qin; Yuhao Liu; Lijie Ma; Shouqin Zhang; Junjie Wang; Sheng Wang

doi:10.21037/atm-20-3830

Profiles of differentially expressed long noncoding RNAs and messenger RNAs in the myocardium of septic mice

Ann Transl Med. 2021 Feb;9(3):199. doi: 10.21037/atm-20-3830.

Authors

Chengbao Li¹, Yongchao Liu¹, Jing Qin¹, Yuhao Liu¹, Lijie Ma¹, Shouqin Zhang¹, Junjie Wang¹, Sheng Wang¹

Affiliation

¹ Department of Critical Care Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.

Abstract

Background: Sepsis is the primary cause of mortality in the intensive care unit (ICU), mainly due to sepsis-induced dysfunction of essential organs such as the heart and lungs. This study investigated the myocardium's epigenetic characterization from septic mice to identify potential treatment targets for septic myocardial dysfunction.

Methods: Cecal ligation and puncture (CLP) was used to induce sepsis in male C57BL/6 mice. Hearts were collected 24 h after surgery to determine the expression profiles of long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) by microarray. To validate the reliability of microarray results, we randomly chose six differentially expressed lncRNAs for qRT-PCR. Functional mapping of differentially expressed mRNAs was annotated with gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses; lncRNA-mRNA co-expression network was constructed to reveal connections between lncRNAs and mRNAs.

Results: Microarray analysis indicated that 1,568 lncRNAs and 2,166 mRNAs were differentially expressed in the myocardium from septic mice, which was further confirmed by qRT-PCR. KEGG pathway analysis showed that numerous differentially expressed mRNAs were relevant to tumor necrosis factor (TNF) and phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling pathways. Moreover, according to the lncRNA-mRNA co-expression network constructed by the above six lncRNAs and their interacting mRNAs, the co-expression network profiles had 57 network nodes and 134 connections, including 76 positive interactions and 58 negative interactions.

Conclusions: In mouse hearts, sepsis resulted in differential expression of lncRNAs and mRNAs related to TNF and PI3K-Akt signaling pathways, suggesting that lncRNAs and their interacting mRNAs may participate in the pathogenesis of septic myocardial dysfunction by regulating TNF and PI3K-Akt signaling pathways.

Keywords: Sepsis; long noncoding RNAs (lncRNAs); messenger RNAs (mRNAs); microarray; myocardial dysfunction.