Comprehensive Analysis and Co-Expression Network of mRNAs and lncRNAs in Pressure Overload-Induced Heart Failure

Shuping Chen,Tingzhong Wang,Aiqun Ma,Jingwen Zhang,Guodong Yang,Yanbo Xue,Qiong Ma,Ling Bai

doi:10.3389/fgene.2019.01271

Abstract

Aim: Heart failure (HF) is the end stage of various cardiovascular diseases. However, the precise regulation of gene expression profiles and functional mechanisms of long non-coding RNAs (lncRNAs) in HF remain to be elucidated. The present study aimed to identify the differentially expressed profiles and interaction of messenger RNAs (mRNAs) and lncRNAs in pressure overload-induced HF. Methods: Male Sprague-Dawley rats were randomly divided into the HF group and the sham-operated group. HF was induced by the transverse aortic constriction (TAC) surgery. The cardiac expression profiles of mRNAs and lncRNAs in HF were investigated using the microarray. Bioinformatics analyses and co-expression network construction were performed from the RNA sequencing data. Results: The expression profiles of mRNAs and lncRNAs showed significant differences between HF and controls. A total of 147 mRNAs and 162 lncRNAs were identified to be differentially expressed with a fold change of >2 in HF. The relative expression levels of several selected mRNAs and lncRNAs were validated by quantitative PCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that diverse pathways were involved in the molecular mechanisms of cardiac hypertrophy and HF including immune response, smooth muscle contraction, ion transmembrane transport. The mRNA-lncRNA and transcription factors (TFs)-lncRNA co-expression networks were constructed and several genes and TFs were identified as key regulators in the pathogenesis of HF. Further functional prediction showed that the lncRNA NONRATT013999 was predicted to cis-regulate mRNA CDH11, and NONRATT027756 was predicted to trans-regulate HCN4. Conclusion: This study revealed specific expression regulation and potential functions of mRNAs and lncRNAs in pressure overload-induced HF. These results will provide new insights into the underlying mechanisms and potential therapeutic targets for HF.

Highlights

Heart failure (HF) is the end stage of various cardiovascular diseases, with high morbidity and mortality, leading to a significant burden on people’s health (Ponikowski et al, 2016)
MRNA and Long non-coding RNAs (lncRNAs) expression profiles were presented in scatter plots (Figure 2) and volcano plots (Figure 3) as HF group compared to SO group, according to the definition that the threshold value for the significance used to define up-regulation or down-regulation of genes was a fold change of >2, as well as with a P-value of < 0.05
We explored the comprehensive characteristics of messenger RNAs (mRNAs) and lncRNAs in pressure overload-induced HF

Summary

Introduction

Heart failure (HF) is the end stage of various cardiovascular diseases, with high morbidity and mortality, leading to a significant burden on people’s health (Ponikowski et al, 2016). LncRNAs are found to combine other RNAs or DNAs and have complicated transcriptional or post-transcriptional regulatory functions (Mercer et al, 2009; Geisler and Coller, 2013). These RNAs have been shown to play potential roles in many physiological and pathological processes of cardiovascular diseases (Uchida and Dimmeler, 2015; Bar et al, 2016). While there are scarcely any comprehensive research and functional analysis of messenger RNAs (mRNAs) and lncRNAs in HF induced by pressure overload, and the underlying mechanisms and pathways remain poorly understood

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