Integrated microRNA and mRNA Expression Profiling Identifies Novel Targets and Networks Associated with Ebstein's Anomaly.

Masood Abu-Halima,Eckart Meese,Basim M Ayesh,Mohammed Abd El-Rahman,Hashim Abdul-Khaliq,Viktoria Wagner,Lea Simone Becker,Ulrike Fischer

doi:10.3390/cells10051066

Abstract

Little is known about abundance level changes of circulating microRNAs (miRNAs) and messenger RNAs (mRNA) in patients with Ebstein’s anomaly (EA). Here, we performed an integrated analysis to identify the differentially abundant miRNAs and mRNA targets and to identify the potential therapeutic targets that might be involved in the mechanisms underlying EA. A large panel of human miRNA and mRNA microarrays were conducted to determine the genome-wide expression profiles in the blood of 16 EA patients and 16 age and gender-matched healthy control volunteers (HVs). Differential abundance level of single miRNA and mRNA was validated by Real-Time quantitative PCR (RT-qPCR). Enrichment analyses of altered miRNA and mRNA abundance levels were identified using bioinformatics tools. Altered miRNA and mRNA abundance levels were observed between EA patients and HVs. Among the deregulated miRNAs and mRNAs, 76 miRNAs (49 lower abundance and 27 higher abundance, fold-change of ≥2) and 29 mRNAs (25 higher abundance and 4 lower abundance, fold-change of ≥1.5) were identified in EA patients compared to HVs. Bioinformatics analysis identified 37 pairs of putative miRNA-mRNA interactions. The majority of the correlations were detected between the lower abundance level of miRNA and higher abundance level of mRNA, except for let-7b-5p, which showed a higher abundance level and their target gene, SCRN3, showed a lower abundance level. Pathway enrichment analysis of the deregulated mRNAs identified 35 significant pathways that are mostly involved in signal transduction and cellular interaction pathways. Our findings provide new insights into a potential molecular biomarker(s) for the EA that may guide the development of novel targeting therapies.

Highlights

IntroductionWith an average prevalence of ~1 per 200,000 live births, accounting for ~1% of all birth defects [1]
Integrative analysis resulted in 37 interactions between the identified 19 miRNAs and 14 target messenger RNAs (mRNA) that showed fold change values ≥ 2.0 and ≥ 1.5 and significantly high correlation differences between the Ebstein’s anomaly (EA) patient group and the healthy control volunteers (HVs) (Figure 4)
Abundance levels of certain miRNA and mRNA in the blood of EA patients differ from HVs (Figure 2A,B)

Summary

Introduction

With an average prevalence of ~1 per 200,000 live births, accounting for ~1% of all birth defects [1]. It is characterized by an abnormal formation of the tricuspid valve and right ventricular myopathy leading to structural and functional abnormalities [2]. The manifestation of tricuspid anomaly depends largely on the severity of the defects and other associated cardiac abnormalities and is associated with the clinical course of patients with EA. Surgical repair or replacement of the tricuspid valve is the most commonly performed cardiac operation to restore normal blood flow and preserve the function of the heart muscle

Methods

Results

Conclusion