NGS-identified circulating miR-375 as a potential regulating component of myocardial infarction associated network. (August 2018)

• Record Type: Journal Article
• Authors: Baulina, Natalia; Osmak, German; Kiselev, Ivan; Matveeva, Natalia; Kukava, Nino; Shakhnovich, Roman; Kulakova, Olga; Favorova, Olga
• Is Part Of: Journal of molecular and cellular cardiology. Volume 121(2018)
• Page Start: 173
• Page End: 179
• Publication Date: 2018-08
• Subjects: Myocardial infarction -- RNA-seq -- Circulating miRNAs -- miR-208b -- miR-375 -- Disease module; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2018.07.129
• Languages: English
• ISSNs: 0022-2828

Abstract

Abstract: Acute myocardial infarction (MI), the most severe type of coronary heart disease, is a leading cause of disability and mortality worldwide. In order to investigate the involvement of miRNAs in the pathologic processes related to MI, we performed the analysis of circulating miRNAs - stable short noncoding RNA molecules - in the peripheral blood plasma of MI patients compared to healthy controls (all persons were men and lived in European Russia) using next generation sequencing. We observed 20 miRNAs, which levels in plasma more than two-fold differed in MI patients ( p < 0.05). Among them miR-208b and miR-375 passed threshold for multiple corrections (FC = 49.2, FDR-adjusted p -value = 0.0078 and FC = −6.4, FDR-adjusted p -value = 0.00076, respectively); these data were then validated using RT-qPCR (FC = 5.3, p -value = 0.028 and FC = −2.1, p -value = 0.0039, respectively). While for miR-208b we reidentified earlier observations, miR-375 was found to be associated with MI for the first time. To investigate the reasons for which miR-375 holds a special place among circulating miRNAs in MI, enrichment and network analyses of miR-375 target genes and their interactions were carried out. PIK3CA and TP53 genes, regulated by miR-375, were identified as the key players of MI disease module. Graphical abstract: Highlights: MiR-375 decreased level was shown in plasma of MI patients the day after disease onset. Concomitantly, miR-208b increased level was reidentified in plasma of MI patients. Gene set enrichment and network analyses found miR-375 target genes involved in MI. PIK3CA and TP53 genes, regulated by miR-375, were found as the key players of MI disease module.