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MiR-155-5p accelerates cerebral ischemia-reperfusion injury via targeting DUSP14 by regulating NF-κB and MAPKs
1Department of Neurology, Xuzhou Cancer Hospital, Xuzhou City, Jiangsu Province, China. YuShisrt@163.com.
Objective:
This study aimed to explore the role of miR-155-5p in middle cerebral artery occlusion/reperfusion (MCAO/R) model in rats and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced SH-SY5Y cells. In addition, this study also aimed to explore the underlying mechanisms to expect that miR-155-5p may be investigated as a new and effective diagnostic and therapeutic target for ischemic stroke.
Materials And Methods:
The in vivo MCAO/R rat model and in vitro OGD/R cell model were established. The miR-155-5p mRNA expression was detected by quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). Dual specificity ATPase (DUSP) 14 was predicted to be a potential target of miR-155-5p by TargetScan. The targeting relationship was confirmed by Luciferase assay. The cell viability was determined using the Cell Counting Kit-8 (CCK-8). The expression level of inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) levels were detected by Enzyme-Linked Immunosorbent Assay (ELISA). Western blot was used to detect the protein expression of DUSP14, the apoptotic protein Cleaved cysteine-aspartic acid protease (caspase)-3, and Cleaved PARP, as well as nuclear factor kappa B (NF-κB) and MAPKs signaling pathways related proteins.
Results:
MiR-155-5p was upregulated in both MCAO/R rats and OGD/R-induced SH-SY5Y cells. MiR-155-5p knockdown inhibited OGD/R-induced cell injury and inflammation, as well as MCAO/R-induced brain injury. MiR-155-5p regulated the NF-κB and MAPKs signaling pathways by targeting DUSP14. DUSP14 knockdown partially reversed the protective effect of miR-155-5p knockdown on OGD/R-induced SH-SY5Y cell injury and inflammation.
Conclusions:
MiR-155-5p accelerates cerebral I/R injury via targeting DUSP14 by regulating NF-κB and MAPKs signaling pathways. Inhibition of miR-155-5p significantly reduces apoptosis and brain injury. These results indicated that miR-155-5p plays a key role in cerebral I/R injury and has the potential to be explored as a new target for ischemic stroke.
Insights
MicroRNA-155-5p (miR-155-5p) accelerates cerebral ischemia-reperfusion injury by targeting DUSP14 and activating inflammatory pathways. Inhibiting miR-155-5p reduces brain injury and apoptosis, suggesting its potential as a therapeutic target for ischemic stroke.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Ischemic stroke is a leading cause of death and disability worldwide.
- Cerebral ischemia-reperfusion (I/R) injury exacerbates stroke-induced brain damage.
- MicroRNAs (miRNAs) play critical roles in regulating cellular processes, including those involved in I/R injury.
Purpose of the Study:
- To investigate the role of miR-155-5p in cerebral I/R injury using rat models and cell cultures.
- To elucidate the underlying molecular mechanisms by which miR-155-5p influences I/R injury.
- To evaluate miR-155-5p as a potential diagnostic and therapeutic target for ischemic stroke.
Main Methods:
- Established in vivo middle cerebral artery occlusion/reperfusion (MCAO/R) rat models and in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) SH-SY5Y cell models.
- Quantified miR-155-5p expression using qRT-PCR.
- Identified Dual Specificity Phosphatase 14 (DUSP14) as a target of miR-155-5p via TargetScan and confirmed with luciferase assays.
- Assessed cell viability (CCK-8), inflammatory cytokine levels (ELISA), and protein expression (Western blot) of DUSP14, apoptosis markers (caspase-3, PARP), and signaling pathway proteins (NF-κB, MAPKs).
Main Results:
- miR-155-5p was significantly upregulated in both MCAO/R rats and OGD/R cells.
- Knockdown of miR-155-5p reduced OGD/R-induced cell injury, inflammation, and MCAO/R-induced brain damage.
- miR-155-5p targeted DUSP14, modulating NF-κB and MAPKs signaling pathways.
- DUSP14 knockdown partially counteracted the protective effects of miR-155-5p inhibition.
Conclusions:
- miR-155-5p exacerbates cerebral I/R injury by targeting DUSP14 and regulating NF-κB and MAPKs signaling pathways.
- Inhibiting miR-155-5p demonstrates significant neuroprotective effects by reducing apoptosis and brain injury.
- miR-155-5p represents a promising therapeutic target for ischemic stroke treatment.
