Micro-RNA signatures in monozygotic twins discordant for congenital heart defects


Autoři: Masood Abu-Halima aff001;  Josephin Weidinger aff002;  Martin Poryo aff002;  Dominic Henn aff003;  Andreas Keller aff004;  Eckart Meese aff001;  Hashim Abdul-Khaliq aff002
Působiště autorů: Institute of Human Genetics, Saarland University, Homburg/Saar, Germany aff001;  Department of Pediatric Cardiology, Saarland University Medical Center, Homburg/Saar, Germany aff002;  Department of Hand, Plastic and Reconstructive Surgery, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany aff003;  Chair for Clinical Bioinformatics, Saarland University, Saarbruecken, Germany aff004
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pone.0226164

Souhrn

Background

MicroRNAs (miRNAs) are small RNAs regulating gene expression post-transcriptionally. Recent studies demonstrated that miRNAs are involved in the development of congenital heart defects (CHD). In this study, we aimed at identifying the specific patterns of miRNAs in blood of monozygotic twin pairs discordant for CHD and to assess whether miRNAs might be involved in the development or reflect the consequences of CHD.

Methods

miRNA microarray analysis and Real-Time Quantitative PCR (RT-qPCR) were employed to determine the miRNA abundance level from 12 monozygotic twins discordant for CHD and their non-CHD co-twins (n = 12). Enrichment analyses of altered miRNAs were performed using bioinformatics tools.

Results

Compared with non-CHD co-twins, profiling analysis indicated 34 miRNAs with a significant difference in abundance level (p<0.05, fold change ≥ 1.3), of which 11 miRNAs were up-regulated and 23 miRNAs were down-regulated. Seven miRNAs were validated with RT-qPCR including miR-511-3p, miR-1306-5p, miR-421, miR-4707-3p, miR-4732-3p, miR-5189-3p, and miR-890, and the results were consistent with microarray analysis. Five miRNAs namely miR-511-3p, miR-1306-5p, miR-4732-3p, miR-5189-3p, and miR-890 were found to be significantly up-regulated in twins < 10 years old. Bioinformatics analysis showed that the 7 validated miRNAs were involved in phosphatidylinositol signaling, gap junction signaling, and adrenergic signaling in cardiomyocytes.

Conclusions

Our data show deregulated miRNA abundance levels in the peripheral blood of monozygotic twins discordant for CHD, and identify new candidates for further analysis, which may contribute to understanding the development of CHD in the future. Bioinformatics analysis indicated that the target genes of these miRNAs are likely involved in signaling and communication of cardiomyocytes.

Klíčová slova:

Blood – Congenital heart defects – Microarrays – MicroRNAs – Monozygotic twins – Twins – Ventricular septal defects


Zdroje

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Článok vyšiel v časopise

PLOS One


2019 Číslo 12