Clinical Significance of miR-28-5p in Ischemic Stroke and Its Neuroprotective Effect after Ischemia-Reperfusion
Zhu Li1, Jianchang Mu2, Hongfei Yang3
1Emergency Department, The Second Affiliated Hospital of Zunyi Medical University, Guizhou, China.
Introduction:
Ischemic stroke (IS) remains a leading cause of global morbidity and mortality, necessitating novel therapeutic targets. MicroRNAs show promise in modulating post-stroke pathology, yet the role of miR-28-5p in IS remains unexplored. This study aimed to investigate miR-28-5p expression in IS and its clinical and mechanistic significance.
Methods:
Serum miR-28-5p levels were quantified via qRT-PCR in 129 IS patients and 97 healthy controls. Kaplan-Meier (K-M) analysis and multivariate COX regression analysis evaluated the prognostic value of miR-28-5p in IS. In vitro, dual-luciferase assays validated the interaction between miR-28-5p and WNK3. Oxygen-glucose deprivation/reoxygenation (OGD/R)-treated HMC3 microglia were used to assess miR-28-5p/WNK3 axis in microglial polarization, oxidative stress, and inflammation.
Results:
Serum miR-28-5p was significantly downregulated in IS patients, associated with elevated triglycerides, low-density lipoprotein cholesterol, reduced high-density lipoprotein cholesterol levels, and higher NIHSS scores. K-M analysis revealed a lower progression-free survival rate in IS patients with low miR-28-5p expression, and COX regression analysis confirmed miR-28-5p as an independent prognostic factor. In mechanism miR-28-5p directly targeted WNK3. Overexpression of miR-28-5p suppressed OGD/R-induced M1 polarization, oxidative stress (reduced malondialdehyde, elevated superoxide dismutase), and inflammatory cytokines (decreased TNF-α, IL-6, IL-1β, and increased IL-10), whereas WNK3 overexpression reversed these effects.
Conclusion:
MiR-28-5p served as a diagnostic biomarker and independent prognostic factor in IS. Its neuroprotection involved suppressing WNK3-mediated microglial M1 polarization, oxidative stress, and inflammation, highlighting its potential as a therapeutic target for IS.
Insights
MicroRNA-28-5p is downregulated in ischemic stroke (IS) patients and acts as a diagnostic biomarker. This microRNA (miRNA) shows neuroprotective effects by inhibiting WNK3, reducing inflammation and oxidative stress in IS.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Ischemic stroke (IS) is a major cause of death and disability worldwide.
- Novel therapeutic targets for IS are urgently needed.
- MicroRNAs (miRNAs) are implicated in post-stroke pathology, but miR-28-5p's role is unknown.
Purpose of the Study:
- Investigate miR-28-5p expression in IS patients.
- Determine the clinical significance and prognostic value of miR-28-5p in IS.
- Elucidate the underlying mechanisms of miR-28-5p in IS pathology.
Main Methods:
- Quantified serum miR-28-5p levels using qRT-PCR in 129 IS patients and 97 controls.
- Assessed prognostic value via Kaplan-Meier and COX regression analyses.
- Validated miR-28-5p targeting of WNK3 using dual-luciferase assays and studied its effects on microglial polarization, oxidative stress, and inflammation in vitro.
Main Results:
- Serum miR-28-5p was significantly lower in IS patients, correlating with lipid profiles and stroke severity (NIHSS).
- Low miR-28-5p predicted poorer progression-free survival (PFS) and was an independent prognostic factor.
- miR-28-5p directly targeted WNK3, suppressing OGD/R-induced M1 microglial polarization, oxidative stress, and pro-inflammatory cytokines.
Conclusions:
- miR-28-5p functions as a diagnostic biomarker and independent prognostic factor for IS.
- Neuroprotection by miR-28-5p involves inhibiting WNK3, thereby reducing microglial M1 polarization, oxidative stress, and inflammation.
- miR-28-5p represents a potential therapeutic target for ischemic stroke.
Related Concept Videos
01:15Ischemic Stroke l: Introduction
01:15Ischemic Stroke ll: Pathophysiology