Abstract WMP117: Altered Patterns of microRNA 9-3p in Acute Ischemic Stroke With Large Vessel Occlusion

Abstract

Background: Stroke is a significant health issue in the United States, and identifying biomarkers for preventing acute ischemic stroke (AIS) remains the highest priority. This study aims to identify microRNA (miRNA) associated with AIS pathophysiology through longitudinal and case-control studies. Methods: We examined global miRNA profiles of serum exosome vesicles of 15 patients with a large vessel occlusion (LVO) using NextGen sequencing. Discovery cohort consisted of miRNA profiles collected during acute (<72 hours, T1) and chronic (3-5 months, T2) stroke stages. The preliminary results were validated through Validation set-1 included 55 LVO cases and 53 controls. and Validation set-2 comprised 15 LVO patients collected at different time points <24h-A1, 48-72h-A2, 5-7 days-A3, >3 months-A4. Results: Our study identified four miRNAs, miR-9-3p, miR-129-5p, miR-223-3p, and miR-423-5p, with differential expressions in LVOs compared to controls. Exosomal miR-9-3p showed a 14.7-fold increase in T1 (Bonferroni p= 9.4x10 -6 ) in the Discovery set and a 9.39-fold increase (Bonferroni p= 1.3x10 -4 ) in stroke cases compared to controls in the Validation-set-1. In the longitudinal analysis of Validation set-2, miR-9-3p levels peaked significantly at A2 and then gradually decreased over A3 and A4 time points. Though miR-129-5p and miR-423-5p were also significantly upregulated during the T1, their association did not survive the stringent Bonferroni correction in any sets. Discussion and Conclusion: MiR-9-3p triggers brain injury via caspase pathway in the murine stroke model. Its role in human AIS pathophysiology is not available. For the first time, we report the possible contribution of miR-9-3p during the acute state in LVO strokes. The pathway analysis suggests miR-9-3p may lead to neuronal cell death and apoptosis in AIS. If confirmed, therapeutic targeting of miRNA 9-3p may become clinically useful biomarkers for treating LVO in humans. Funding: College of Medicine Alumni Association, the Presbyterian Health Foundation, Leinbach Foundation grants, and Dr. Geoffrey Altshuler Endowment funds from the Children’s Health Foundation of OUHSC, and partly supported by National Institute of Health (NIH/NIDDK) R01DK118427 grant.