Bioinformatic Exploration of Circulating microRNAs Related to Functional Outcomes in Patients With Acute Ischemic Stroke: An Exploratory Prospective Study

Abstract

Background Although epigenetic modifications have been expected to play an important role in neuroplasticity for stroke recovery, the role of dynamic microRNA (miRNA) regulation related to functional outcomes after ischemic stroke remains unclear. Therefore, the current study performed a comprehensive miRNA expression analysis in serum to identify specifically altered circulating miRNAs associated with different grades of functional outcomes in patients with acute ischemic stroke (AIS). Methods Twelve patients with AIS in the middle cerebral artery region were included in this study. Peripheral blood samples were collected from patients one or two days after hospitalization. Total RNA, including small RNAs, was extracted from 400 µL of serum, and comprehensive miRNA expression analysis was performed to identify specifically altered circulating miRNAs associated with different grades of functional outcomes. Functional outcomes were evaluated three months after stroke onset using the modified Rankin Scale (mRS), classified as favorable (mRS score of 0 or 1) or unfavorable (mRS score of 2 to 5). Differentially expressed miRNAs were analyzed using the DESeq2 package. Target genes of the miRNAs were explored using miRTargetLink 2.0. Results Acute miRNA expression dynamics were characterized by differences in the patients' functional outcomes following ischemic stroke. The favorable outcome group exhibited significantly downregulated miRNAs, including hsa-miR-218-1, hsa-miR-218-2, hsa-miR-320e, hsa-miR-320d-1, hsa-miR-320d-2, hsa-miR-326, and hsa-miR-4429. In addition, 15 miRNAs, including hsa-miR-223, hsa-miR-18a, hsa-miR-411, and hsa-miR-128-1, were significantly upregulated in the favorable outcome group compared to the unfavorable outcome group. Interesting and strong validated networks between miRNAs and their target genes were identified. Conclusion This study identified specifically altered circulating miRNAs in serum associated with varying grades of functional outcomes in AIS patients and explored miRNA-target gene networks that might contribute to these outcomes. Although further studies are needed, this study highlights their potential role as biomarkers for predicting functional outcomes in patients with AIS.

Keywords: acute ischemic stroke; bioinformatics; functional outcome; microrna; serum.