Cardiovascular

Diagnostic and Prognostic Significance of Aberrant miR-508-3p Expression in Acute Ischemic Stroke.

TL;DR

Downregulated serum miR-508-3p is associated with AIS severity, inflammation, and poor prognosis, suggesting its diagnostic and prognostic potential, with its protective effect possibly involving targeting SOCS3 and alleviating brain microvascular endothelial cell injury.

Key Findings

Serum miR-508-3p expression was significantly decreased in acute ischemic stroke patients compared to healthy controls.

  • 131 AIS patients were compared to 125 healthy controls
  • The difference in miR-508-3p expression was statistically significant (p < 0.001)
  • Expression was detected using quantitative real-time polymerase chain reaction (qRT-PCR)
  • Patients were admitted between January 2023 and December 2024

Serum miR-508-3p levels were negatively correlated with stroke severity and inflammatory markers.

  • miR-508-3p was negatively correlated with National Institutes of Health Stroke Scale (NIHSS) score (p < 0.001)
  • Negative correlations were also found with IL-6, IL-1β, TNF-α, and CRP levels (all p < 0.001)
  • Inflammatory marker concentrations were assessed using enzyme-linked immunosorbent assay (ELISA)
  • Lower miR-508-3p corresponded to higher levels of all four inflammatory markers measured

ROC analysis demonstrated that serum miR-508-3p has significant diagnostic value for acute ischemic stroke.

  • Area under the curve (AUC) was 0.8641 (95% CI: 0.8184–0.9098)
  • Sensitivity was 87.79% and specificity was 72.80%
  • Analysis was performed using receiver operating characteristic (ROC) methodology
  • These values suggest moderate-to-high diagnostic accuracy for distinguishing AIS patients from healthy individuals

Low serum miR-508-3p was identified as an independent predictor of poor 90-day prognosis in AIS patients.

  • Multivariate logistic regression was used to identify independent predictors
  • Odds ratio for low miR-508-3p predicting poor 90-day outcome was 0.002 (95% CI: 0.000–0.581, p = 0.032)
  • Prognosis was evaluated using Kaplan-Meier methods in addition to multivariate analysis
  • The 90-day outcome timepoint was used as the prognostic endpoint

miR-508-3p overexpression protected human brain microvascular endothelial cells from oxygen-glucose deprivation/reoxygenation injury in vitro.

  • Human brain microvascular endothelial cells (HBMECs) were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to model ischemic injury
  • miR-508-3p overexpression enhanced cell viability as measured by CCK-8 assay
  • LDH release (a marker of cell injury) was reduced following miR-508-3p overexpression
  • Apoptosis was assessed by flow cytometry and was reduced in miR-508-3p overexpressing cells

miR-508-3p was confirmed to directly target the 3'UTR of the SOCS3 gene using a dual-luciferase reporter assay.

  • A dual-luciferase reporter system was used to confirm targeted binding
  • miR-508-3p binds to the 3' untranslated region (3'UTR) of suppressor of cytokine signaling 3 (SOCS3)
  • SOCS3 is a known regulator of cytokine signaling pathways relevant to inflammation
  • This mechanistic finding suggests a molecular pathway by which miR-508-3p may exert its protective effects

What This Means

This research suggests that a small RNA molecule called miR-508-3p, which circulates in the blood, is significantly reduced in people who have experienced an acute ischemic stroke (a stroke caused by a blocked blood vessel in the brain) compared to healthy individuals. The study enrolled 131 stroke patients and 125 healthy controls and found that patients with lower miR-508-3p levels also tended to have more severe strokes and higher levels of inflammatory proteins in their blood, including IL-6, IL-1β, TNF-α, and CRP. A blood test measuring miR-508-3p showed reasonably good ability to identify stroke patients, correctly identifying about 88% of stroke cases, which hints at its potential usefulness as a diagnostic biomarker. The study also found that patients with lower miR-508-3p levels were more likely to have poor outcomes 90 days after their stroke, even after accounting for other factors, suggesting it may help doctors identify which patients are at higher risk of a bad recovery. In laboratory experiments, artificially increasing miR-508-3p levels in brain blood vessel cells protected those cells from damage mimicking stroke conditions — the cells survived better, showed less injury, and had lower rates of programmed cell death. The researchers also identified that miR-508-3p appears to work by interacting with a gene called SOCS3, which is involved in controlling inflammation. This research suggests that miR-508-3p could serve as both a diagnostic tool for detecting acute ischemic stroke and a prognostic marker for predicting patient recovery. The laboratory findings point to a potential biological mechanism involving inflammation control in brain blood vessels, which could be relevant for future research into stroke treatments. However, these findings would need to be validated in larger and more diverse patient populations before any clinical applications could be considered.

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Citation

Zhang S, Zuo W, Wang D, Huang W, Wang Z, Jin Y, et al.. (2026). Diagnostic and Prognostic Significance of Aberrant miR-508-3p Expression in Acute Ischemic Stroke.. Journal of visualized experiments : JoVE. https://doi.org/10.3791/71815