Inhibition of miR-140-5p attenuates OGD/R-induced neuronal injury by targeting IL1RAPL1
- 1Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- 2Department of Geriatric Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
Abstract
ObjectiveCerebral ischemia–reperfusion (I/R) injury is a major contributor to neuronal damage and long-term neurological dysfunction after stroke. Our previous studies demonstrated that miR-140-5p expression is markedly upregulated following cerebral ischemia and that in vivo overexpression of miR-140-5p exacerbates cognitive impairment, suppresses neurogenesis, and promotes neuronal death in ischemic mouse models; however, its molecular mechanisms remain unclear. This study aimed to investigate the downstream molecular targets of miR-140-5p and to elucidate the mechanisms by which miR-140-5p regulates neuronal injury after I/R.MethodsWe established an oxygen–glucose deprivation/reoxygenation (OGD/R) model in primary cortical neurons and assessed viability via Cell Counting Kit-8 (CCK-8). miR-140-5p expression after OGD/R was examined, and loss-of-function experiments evaluated the effects of miR-140-5p inhibition. Synaptic integrity was assessed by immunofluorescence, and inflammatory cytokines by enzyme-linked immunosorbent assay (ELISA). Proteomic analysis identified potential downstream targets, which were validated via Western blotting and dual-luciferase reporter assays.ResultsWe found that miR-140-5p expression was significantly upregulated in mouse cortical neurons after OGD/R. Functional inhibition of miR-140-5p markedly enhanced neuronal survival, promoted synaptic remodeling, and attenuated inflammatory responses following OGD/R injury. Mechanistically, miR-140-5p was shown to directly target Il1rapl1 and modulate downstream c-Jun N-terminal kinase (JNK) signaling, thereby regulating neuronal viability, inflammation, and synaptic plasticity under ischemia–reperfusion conditions.ConclusionThis study reveals a novel miR-140-5p–mediated regulatory mechanism in neuronal injury following cerebral ischemia–reperfusion and suggests a potential therapeutic target for ischemic brain injury.
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BibTeX
@article{song2026inhibition,
title = {{Inhibition of miR-140-5p attenuates OGD/R-induced neuronal injury by targeting IL1RAPL1}},
author = {Yuan-yue Song and Yuan-yue Song and Zhu-jun Chen and Heng-yu Yan and Li-li Zeng},
journal = {Frontiers in Molecular Neuroscience},
year = {2026},
month = oct,
doi = {10.3389/fnmol.2026.1972044},
url = {https://doi.org/10.3389/fnmol.2026.1972044},
note = {CC BY},
}
RIS
TY - JOUR
TI - Inhibition of miR-140-5p attenuates OGD/R-induced neuronal injury by targeting IL1RAPL1
AU - Yuan-yue Song
AU - Yuan-yue Song
AU - Zhu-jun Chen
AU - Heng-yu Yan
AU - Li-li Zeng
PY - 2026
DA - 2026/10/23
JO - Frontiers in Molecular Neuroscience
DO - 10.3389/fnmol.2026.1972044
UR - https://doi.org/10.3389/fnmol.2026.1972044
AB - ObjectiveCerebral ischemia–reperfusion (I/R) injury is a major contributor to neuronal damage and long-term neurological dysfunction after stroke. Our previous studies demonstrated that miR-140-5p expression is markedly upregulated following cerebral ischemia and that in vivo overexpression of miR-140-5p exacerbates cognitive impairment, suppresses neurogenesis, and promotes neuronal death in ischemic mouse models; however, its molecular mechanisms remain unclear. This study aimed to investigate the downstream molecular targets of miR-140-5p and to elucidate the mechanisms by which miR-140-5p regulates neuronal injury after I/R.MethodsWe established an oxygen–glucose deprivation/reoxygenation (OGD/R) model in primary cortical neurons and assessed viability via Cell Counting Kit-8 (CCK-8). miR-140-5p expression after OGD/R was examined, and loss-of-function experiments evaluated the effects of miR-140-5p inhibition. Synaptic integrity was assessed by immunofluorescence, and inflammatory cytokines by enzyme-linked immunosorbent assay (ELISA). Proteomic analysis identified potential downstream targets, which were validated via Western blotting and dual-luciferase reporter assays.ResultsWe found that miR-140-5p expression was significantly upregulated in mouse cortical neurons after OGD/R. Functional inhibition of miR-140-5p markedly enhanced neuronal survival, promoted synaptic remodeling, and attenuated inflammatory responses following OGD/R injury. Mechanistically, miR-140-5p was shown to directly target Il1rapl1 and modulate downstream c-Jun N-terminal kinase (JNK) signaling, thereby regulating neuronal viability, inflammation, and synaptic plasticity under ischemia–reperfusion conditions.ConclusionThis study reveals a novel miR-140-5p–mediated regulatory mechanism in neuronal injury following cerebral ischemia–reperfusion and suggests a potential therapeutic target for ischemic brain injury.
SN - 1662-5099
ER -