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Establishment of a lncRNA-miRNA-mRNA network in a rat model of atrial fibrosis by whole transcriptome sequencing

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Journal of Interventional Cardiac Electrophysiology Aims and scope Submit manuscript

Abstract

Purpose

Dysregulation of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) plays important roles in atrial fibrillation (AF). This study aimed to identify crucial lncRNAs, miRNAs, and mRNAs in AF based on whole transcriptome sequencing.

Methods

Thirty Sprague Dawley rats were randomly stratified into control and chronic intermittent hypoxia (CIH) groups (n = 15 in each). Hematoxylin-eosin staining, Masson staining, immunohistochemical assay, and western blotting were used to evaluate this model. Thereafter, atrial tissues were sent for whole transcriptome sequencing. Finally, fibrosis-related competing endogenous RNA (ceRNA) regulatory networks were built, and the relative levels of lncRNAs, miRNAs, and mRNAs were validated by real-time quantitative polymerase chain reaction (RT-qPCR) or western blotting.

Results

A CIH-induced atrial fibrosis rat model was successfully constructed. After sequencing, 268 differentially expressed lncRNAs (DELs), 20 differentially expressed miRNAs (DEMs), and 436 differentially expressed genes (DEGs) were identified. Functional analyses showed that these DEGs were associated with several processes and pathways, including “cell division,” “IL-17 signaling pathway,” “NOD-like receptor signaling pathway,” and “cell adhesion molecules.” Fibrosis-related ceRNA networks were then built, comprising five lncRNAs, seven miRNAs, and 19 DEGs. RT-qPCR and western blotting results showed that the patterns of lncRNAs (NONRATT016396.2, NONRATT001596.2, NONRATT011456.2), miRNAs (miR-10b-3p, miR-29b-3p), and mRNAs (Gng7 and Wnt2b) were consistent with sequencing analyses.

Conclusions

The DELs, DEMs, and DEGs identified in this study may participate in atrial fibrosis processes, and the occurrence and progression of AF.

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Data availability

I confirm I have included a Data Availability Statement in my manuscript. BioProject: PRJNA786466

Abbreviations

AF:

atrial fibrillation

CIH:

chronic intermittent hypoxia

lncRNAs:

long non-coding RNAs

miRNAs:

microRNAs

ceRNA:

competing endogenous RNAs

GO:

Gene Ontology

KEGG:

Kyoto Encyclopedia of Genes and Genomes

log2 FC:

log2 fold change

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Funding

This work was supported by the National Natural Science Foundation of China Youth Science Foundation Project (No. 81700304, No. 82000313), Tianjin Natural Science Foundation (No. 16KPXMSF00140, No. 18JCYBJC92200), The Scientific Research Fund Project of Key Laboratory of Second Hospital of Tianjin Medical University (No. 2019ZDSYS02, No. 2019ZDSYS07, No. 2019ZDSYS10, No. 2019ZDSYS11), The Research Fund for Central Laboratory of Second Hospital of Tianjin Medical University (No. 2020YDEY05), The Science & Technology Development Fund of Tianjin Education Commission for Higher Education (No. 2020KJ168), and The PhD Research Foundation of Affiliated Hospital of Jining Medical University (No. 2021-BS-005).

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Authors and Affiliations

  1. Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, the Second Hospital of Tianjin Medical University, Tianjin, 300211, China

    Bo Zhao, Weiding Wang, Yu Liu, Siyu Guan, Wenfeng Shangguan, Shuai Miao, Xiaowei Zhang, Enzhao Liu & Xue Liang

  2. Department of Radiology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, China

    Bo Zhao & Huijia Liu

  3. Department of Cardiology, Affiliated Hospital of Jining Medical University, Jining, 272000, Shandong, People’s Republic of China

    Manman Wang

  4. Department of Geriatric, The Second Hospital of Tianjin Medical University, Tianjin, 300211, China

    Fang Song

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  1. Bo Zhao
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Corresponding authors

Correspondence to Enzhao Liu or Xue Liang.

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All animal studies were conducted in compliance with guidelines from the Animal Administration Committee of Tianjin Medical University (approval number: TMUaMEC2016012).

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The authors declare no competing interests.

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Bo Zhao, Weiding Wang, and Yu Liu are co-first authors.

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Zhao, B., Wang, W., Liu, Y. et al. Establishment of a lncRNA-miRNA-mRNA network in a rat model of atrial fibrosis by whole transcriptome sequencing. J Interv Card Electrophysiol 63, 723–736 (2022). https://doi.org/10.1007/s10840-022-01120-4

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  • DOI: https://doi.org/10.1007/s10840-022-01120-4

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