Long noncoding RNAs and novel inflammatory genes determined by RNA sequencing in human lymphocytes are up-regulated in permanent atrial fibrillation.

Abstract

Atrial fibrillation (AF) is a common arrhythmia in clinical practice. Currently, approximately 33.5 million individuals are affected by AF globally. AF involves multiple complicated mechanisms which have not been fully investigated yet. RNA sequencing (RNAseq) is an outstanding method for investigation of diseases due to its high-throughput information. Here, RNAseq was applied to determine mRNA and long noncoding RNA (lncRNA) expression profiles in human lymphocytes from 6 permanent atrial fibrillation (pmAF) patients and 6 healthy controls. Quantitative real-time PCR (qRT-PCR) was applied to further validate 3 lncRNAs and 4 inflammatory mRNAs. It was discovered that there were numerous differentially-expressed mRNAs and lncRNAs between these two groups. GO analysis indicated that differentially-expressed mRNAs were mainly involved in native immunity, inflammation, signaling transduction and so forth, and they were also enriched in pathways like TNF signaling pathway, NF-kappa B signaling pathway, Toll-like receptor pathway and NOD-like receptor pathway. Moreover, co-expression network demonstrated that dysregulated mRNAs and lncRNAs in pmAF lymphocytes participated in inflammation, autophagy, mitochondrial functions, oxidative stress, etc. Further validation by qRT-PCR demonstrated mRNAs and lncRNAs were significantly higher in lymphocytes from pmAF patients compared with controls. In conclusion, mRNA and lncRNA expression profiles in lymphocytes are significantly different between pmAF and controls, differentially-expressed mRNAs and lncRNAs are involved in pathways closely associated with inflammation, oxidative stress, autophagy, cell apoptosis and collagen synthesis, suggesting lymphocytes might play indispensable roles in the development of pmAF.