NGS-identified circulating miR-375 as a potential regulating component of myocardial infarction associated network

Area of Science:

• Cardiovascular Biology
• Molecular Diagnostics
• Biomarker Discovery

Background:

• Acute myocardial infarction (MI) is a major global health concern, driving significant disability and mortality.
• Understanding the molecular mechanisms underlying MI is crucial for developing effective diagnostic and therapeutic strategies.
• MicroRNAs (miRNAs) are emerging as important regulators in cardiovascular disease pathogenesis.

Purpose of the Study:

• To investigate the role of circulating miRNAs in the pathological processes of acute myocardial infarction.
• To identify novel miRNA biomarkers associated with MI in peripheral blood plasma.
• To explore the functional significance of identified miRNAs in MI pathogenesis.

Main Methods:

• Next-generation sequencing of circulating miRNAs in plasma from male MI patients and healthy European Russian controls.
• Differential expression analysis to identify miRNAs with significant fold changes (p < 0.05).
• Validation of key miRNA candidates using quantitative reverse transcription polymerase chain reaction (RT-qPCR).
• Enrichment and network analyses to elucidate the functional targets of identified miRNAs.

Main Results:

• Twenty circulating miRNAs showed significant differential expression (>2-fold change) in MI patients compared to controls.
• miR-208b and miR-375 were significantly altered, with miR-208b showing a 49.2-fold increase and miR-375 a 6.4-fold decrease.
• Validation confirmed elevated miR-208b (5.3-fold) and decreased miR-375 (-2.1-fold) in MI patients.
• miR-375 was identified as a novel circulating biomarker associated with MI for the first time.
• Network analysis implicated PIK3CA and TP53, regulated by miR-375, as key players in the MI disease module.

Conclusions:

• Circulating miRNAs, particularly miR-208b and the novel biomarker miR-375, are significantly altered in acute myocardial infarction.
• miR-375's association with MI, potentially through regulation of PIK3CA and TP53, offers new insights into disease mechanisms.
• These findings highlight the potential of circulating miRNAs as diagnostic biomarkers and therapeutic targets for MI.