miR-10a in Peripheral Blood Mononuclear Cells Is a Biomarker for Sepsis and Has Anti-Inflammatory Function

Area of Science:

• Biochemistry
• Immunology
• Molecular Biology

Background:

• Recent literature highlights circulating microRNAs (miRNAs) as potential sepsis biomarkers.
• Immune cells are critical in sepsis pathophysiology.
• Sepsis-3 definition criteria are used to differentiate sepsis from infection.

Purpose of the Study:

• To identify specific miRNAs in peripheral blood mononuclear cells (PBMC) capable of distinguishing sepsis from non-septic infection.
• To investigate the role of identified miRNAs in sepsis pathogenesis.

Main Methods:

• Prospective study involving 62 patients (41 sepsis, 21 infection) and 20 healthy controls.
• Quantification of four selected miRNAs (miR-10a, miR-17, miR-27a, miR-125b) in PBMC using qRT-PCR.
• Validation in a mouse model of sepsis (CLP) and THP-1 monocyte cell line.

Main Results:

• Lower miR-10a levels in PBMC of sepsis patients compared to infection and control groups.
• Negative correlation between miR-10a levels and disease severity, C-reactive protein, and procalcitonin.
• miR-10a demonstrated diagnostic value for sepsis and prognostic value for 28-day mortality.
• Increased MAP3K7 (miR-10a target) and NF-κB pathway activation in sepsis PBMC.
• Decreased miR-10a in mouse sepsis model early after CLP.
• Overexpression of miR-10a reduced MAP3K7 and pro-inflammatory cytokines (IL-6, TNF-α, MCP-1) in THP-1 cells.

Conclusions:

• PBMC miR-10a levels are significantly reduced in sepsis and correlate negatively with disease severity.
• miR-10a can differentiate sepsis from infection and predict 28-day mortality.
• miR-10a exhibits an anti-inflammatory role in sepsis pathogenesis.