Integrated Analysis Identifies Key lncRNA-mRNA Network in Atrial Fibrillation

Abstract Background: Atrial fibrillation (AF), the most common cardiac arrhythmias, is associated with the risk of stroke and pronounced morbidity and mortality. The application of biomarkers in the management of AF has been grown as an interesting topic. Long non-coding RNAs (lncRNAs) have been reported to participate in the pathogenesis of cardiovascular diseases by regulating mRNA networks. Results: In this study, we firstly used two AF cohorts to identify circulating lncRNAs and mRNAs with potential diagnostic prediction value. The expression of 8,164 lncRNAs and 14,508 mRNAs were quantified in these two cohorts with lncRNA microarray. By using a stringent threshold (P < 0.01, fold change > 2.0 or < 0.5), we identified 10 lncRNAs and 7 mRNAs were significantly differentially expressed in AF in both cohorts. To further explore the function of these significantly dysregulated lncRNA and mRNA, we performed co-expression analysis by using RNA-seq data of 429 atrial appendage tissue samples. Interestingly, we found a significant lncRNA-mRNA network for 5 lncRNAs (AC109460.1, AL031123.1, MIAT, PTPRG-AS1 and ZNF815P) and 4 mRNAs (D2HGDH, SPNS1, KCND2 and TNFAIP8L3) with Pearson correlation r > 0.3 (all P < 10-8). Moreover, in silico analysis showed that the lncRNA MIAT and PTPRG-AS1 may serve as miRNA sponges to regulate D2HGDH, SPNS1, KCND2 and TNFAIP8L3.Conclusions: Our study suggested that the circulating lncRNA-mRNA network of MIAT and PTPRG-AS1 play an important role in AF and may be considerable diagnostic biomarkers. These results may contribute to the precise diagnosis and early detection of this disease.