404. miRNA-Gene Pairs Associated with Shock and Renal Failure in Filipino Septic Patients

BACKGROUND: Small non-coding microRNAs (miRNAs) are increasingly recognized as key regulators of the host response to sepsis. However, the molecular mechanisms implicated in the role of miRNAs during sepsis progression is still unclear. It is hypothesized that differentially expressed genes in septic patients with worse outcomes are associated with dysregulation of miRNA expression. This study aimed to identify specific miRNA-gene pairs that may be implicated in the development of shock and renal failure in sepsis. METHODS: miRNA from serum and RNA from PBMCs were acquired from n = 40 participants in a prospective cohort of Filipino septic patients: n = 15 developed septic shock and n = 17 developed renal failure. RT-qPCR was done to measure the expression of 21 sepsis-associated miRNAs. Differentially expressed miRNAs (DEMs) for each outcome was identified, followed by gene target prediction for each DEM. Gene expression microarrays covering 18,616 genes were also performed to identify differentially expressed genes (DEGs; P < 0.05, log FC> |0.3|) for each outcome. Significant miRNA-gene pairs were selected by evaluating the overlap of the predicted gene targets of the DEMs with the DEGs for each corresponding outcome. Given the gene-silencing mechanism of miRNAs, overlap analysis was performed on only the downregulated DEGs when the specific DEM was upregulated (and vice versa). RESULTS: Septic participants who developed shock, compared with those who did not, had higher expression of 1 DEM, miR-223-5p, and downregulation of 20 DEGs. NUS1 was the only predicted gene target of miR-223-5p that was also downregulated in septic shock. Participants who developed renal failure, vs. those who did not, had lower expression 6 DEMs and upregulation of 6 DEGs. KPNA4 is a gene target of the DEMs, miR-126-5p, and miR-181a-5p, that was also upregulated in renal failure. CONCLUSION: Significant miRNA–gene pairs related to worse clinical outcomes in sepsis were identified: miR-223-5p with NUS1 for shock and either miR-126-5p or miR-181-5p with KPNA4 for renal failure. While the biological significance of these miRNA-gene pairs still needs to be evaluated, these findings can potentially help future efforts in developing prognostic markers or therapeutic targets for shock and renal failure in sepsis. DISCLOSURES: All authors: No reported disclosures.