Analysis of potential roles of combinatorial microRNA regulation in occurrence of valvular heart disease with atrial fibrillation based on computational evidences

Abstract

Background Atrial fibrillation (AF) is the most common arrhythmia. Patients with valvular heart disease (VHD) frequently have AF. Growing evidence demonstrates that a specifically altered pattern of microRNA (miRNA) expression is related to valvular heart disease with atrial fibrillation (AF-VHD) processes. However, the combinatorial regulation by multiple miRNAs in inducing AF-VHD remains largely unknown. Methods The work identified AF-VHD-specific miRNAs and their combinations through mapping miRNA expression profile into differential co-expression network. The expressions of some dysregulated miRNAs were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The regulations of signaling pathways by the combinatorial miRNAs were predicted by enrichment analysis tools. Results Thirty-two differentially expressed (DE) miRNAs were identified to be AF-VHD-specific, some of which were new findings. These miRNAs interacted to form 5 combinations. qRT-PCR confirmed the different expression of several identified miRNAs, which illustrated the reliability and biomarker potentials of 32 dysregulation miRNAs. The biological characteristics of combinatorial miRNAs related to AF-VHD were highlighted. Twelve signaling pathways regulated by combinatorial miRNAs were predicted to be possibly associated with AF-VHD. Conclusions The AF-VHD-related signaling pathways regulated by combinatorial miRNAs may play an important role in the occurrence of AF-VHD. The work brings new insights into biomarkers and miRNA combination regulation mechanism in AF-VHD as well as further biological experiments.

Combinatorial miRNA1a/15b interference drives adult cardiac regeneration

“…miRNAs are known to play critical roles in cardiac pathophysiology, including MI and heart failure. Most studies have primarily focused on the role of individual miRNAs, although combinatorial activities of miRNAs are being increasingly investigated and recognized in recent years 77,78 . Although the impact of individual miRNA modulation cannot be underestimated, we speculate that more complex processes might necessitate the simultaneous combinatorial modulation of two or more regulatory moieties.…”

<i>BIRC5</i>, <i>GAJ5,</i> and lncRNA NPHP3-AS1 Are Correlated with the Development of Atrial Fibrillation-Valvular Heart Disease

“…Currently, several miRNAs have been identified to be related to AF-VHD, such as hsa-miR-101, hsa-miR-133a, and hsa-miR-29b. 10) However, hsa-miR-1285-3p's effect on AF development has not been searched. Interestingly, it has been uncovered that hsa-miR-1285-3p was dramatically up-regulated in heart and plasma during heart failure.…”

“…For instance, lncRNA PVT1 has been considered to be playing a key role in promoting atrial fibrosis via the miR-128-3p-SP1-TGF-β1-Smad axis in AF. 10) The lncRNA KCNQ1OT1 upregulation regulates angiotensin II-induced AF by regulating the miR-384/CACNA1C axis. 11) Besides, lncRNA GAS5 overexpression could inhibit cell proliferation of AF by suppressing ALK5 expression.…”

“…13,14) Wang, et al analyzed the miRNA regulation in AF-VHD occurrence and identified AF-VHD-specific miRNAs. 10) GSE113013 was analyzed by Rao, et al to explore the lncRNA and mRNA expressions of atrial appendage tissues from SR-VHD and AF-VHD patients. However, the molecular mechanisms underlying the development of VHD to AF-VHD have not yet been understood.…”