Introduction:

Sepsis is a life-threatening disease caused by an excessive immune response to infection, causing inflammation, tissue damage, and organ failure. Globally, sepsis caused 19.7% of all fatalities in 2017, with India having one of the highest rates, with over 4 million cases annually. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression by binding to messenger RNAs (mRNAs) and blocking their transcription. Identifying miRNAs as predictive biomarkers could significantly reduce the worldwide burden of sepsis by enhancing patient care, management, and treatment. This study aims to discover potential diagnostic biomarkers implicated in the dysregulated immune response and provide insights for mechanistic illness progression research.

Methods:

The Gene Expression Omnibus (GEO) datasets GSE134364, GSE134358, GSE94717, GSE236713 and GSE131761 were used to identify the differentially expressed genes involved in sepsis. Biological targets were identified that coincide with the identified differentially expressed miRNAs. The biological pathways were analyzed using KEGG and GO. Hub genes were identified for further functional and signaling pathway analysis.

Results:

Several differentially expressed miRNA biomarkers were identified between the control and sepsis groups (p<0.05 and fold change >2). MiR-146a regulates the immune response, miR-155 promotes pro-inflammatory cytokine expression, miR-150 regulates immune cell function and inflammation, and miR-21 is involved in apoptosis and inflammation. Moreover, we identified matrix metalloproteinase (MMP8 and MMP9) as being involved in neutrophil degranulation.

Conclusion:

MiRNAs regulating MMP-8 and MMP-9 in sepsis regulate immune responses and inflammation, leading to tissue damage. MiR-21 downregulate MMP-9 expression, while miR-146a indirectly affects MMP expression by targeting upstream signaling molecules. Targeting specific miRNAs that regulate MMPs offers a potential therapeutic strategy for managing sepsis. By modulating the levels of these miRNAs, it may be possible to control the activity of MMPs and reduce the harmful effects of excessive inflammation and tissue damage.