Screening and functional analysis of differentially expressed lncRNAs in rapid atrial pacing dog atrial tissue

J Interv Card Electrophysiol. 2021 Aug;61(2):375-384. doi: 10.1007/s10840-020-00824-9. Epub 2020 Jul 15.

Abstract

Purpose: Atrial fibrillation (AF) is one of the most commonly sustained arrhythmias in clinical practice. Long non-coding RNAs (lncRNAs) are gene regulatory elements involved in the development of several diseases. We aimed to explore the expression characteristics of lncRNAs associated with AF.

Methods: We randomly assigned 12 adult healthy mongrel dogs into a control group and an atrial pacing group. Atrial pacing stimulation was performed at a high frequency of 500 beats per min for 14 consecutive days in the atrial pacing group. HE and Masson staining were used to detect rapid atrial pacing induced atrial fibrosis. Total RNA extraction was performed on dog atrial tissues and was used for high-throughput sequencing of lncRNAs.

Results: A total of 10,310 lncRNAs were detected, and 33 differentially expressed lncRNAs were screened. Among them, 19 lncRNAs were upregulated in the atrial pacing group, and 14 lncRNAs were downregulated. Gene Ontology (GO) classification, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and interaction networks showed that AF-related lncRNAs participate in the regulation of AF in diverse biological processes, cellular components, molecular functions, signaling pathways, and complex interactions with miRNAs and mRNAs. Five differentially expressed lncRNAs were selected for RT-PCR validation, and the verification results were consistent with the results of lncRNA sequencing.

Conclusions: In summary, our study enhances our understanding of the biological functions of AF-related lncRNAs by screening and analyzing differentially expressed lncRNAs, and the results help to enrich the theoretical basis for the treatment of atrial fibrillation.

Keywords: Atrial fibrillation; Dog; High-throughput sequencing; Long non-coding RNA; Rapid atrial pacing.

MeSH terms

  • Animals
  • Atrial Fibrillation* / genetics
  • Dogs
  • Heart Atria
  • MicroRNAs*
  • RNA, Long Noncoding* / genetics
  • RNA, Messenger

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Messenger