MiR-7-5p Enhances Cerebral Ischemia-Reperfusion Injury by Degrading sirt1 mRNA
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1Department of Neurology, The 4th Hospital Affiliated Jiangsu University, Zhenjiang City China; and.
Abstract:
Cerebral ischemia-reperfusion (I/R) is a kind of neurovascular disease that causes serious cerebral damage. MicroRNAs (miRNAs) have been widely reported to participate in multiple diseases, including cerebral I/R injury. However, the exact mechanisms of miR-7-5p in cerebral I/R injury was not fully elucidated. In this study, we explored the biological role and regulatory mechanism of miR-7-5p in cerebral I/R injury. We established an in vivo model of cerebral I/R by middle cerebral artery occlusion and an in vitro cellular model of cerebral I/R injury through treating neurons (SH-SY5Y cells) with oxygen-glucose deprivation (OGD). In addition, miR-7-5p expression was confirmed to be upregulated in the cerebral I/R rat model and OGD/R-treated SH-SY5Y cells. Moreover, miR-7-5p inhibition overtly suppressed cerebral injury, cerebral inflammation, and SH-SY5Y cells apoptosis. Sirtuin 1 (sirt1) is previously reported to alleviate I/R, and in this study, it was identified to be a target of miR-7-5p based on luciferase reporter assay. Reverse transcription-quantitative polymerase chain reaction revealed sirt1 expression was downregulated in the cerebral I/R rat model and OGD/R-treated SH-SY5Y cells. Besides, miR-7-5p negatively regulated sirt1. Finally, rescue assays delineated sirt1 overexpression recovered the miR-7-5p upregulation-induced promotion on cerebral I/R injury. In conclusion, miR-7-5p enhanced cerebral I/R injury by degrading sirt1, providing a new paradigm to investigate cerebral I/R injury.
Insights
MicroRNA-7-5p (miR-7-5p) worsens cerebral ischemia-reperfusion injury by downregulating Sirtuin 1 (sirt1). Inhibiting miR-7-5p reduces brain damage and inflammation, offering a potential therapeutic target.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Cerebral ischemia-reperfusion (I/R) injury is a significant cause of neurological damage.
- MicroRNAs (miRNAs) play a role in various diseases, including cerebral I/R injury, but the specific mechanisms of miR-7-5p remain unclear.
Purpose of the Study:
- To investigate the biological role and regulatory mechanism of miR-7-5p in cerebral I/R injury.
- To explore the potential of targeting miR-7-5p for therapeutic interventions in cerebral I/R injury.
Main Methods:
- Established in vivo (middle cerebral artery occlusion) and in vitro (oxygen-glucose deprivation/reoxygenation on SH-SY5Y cells) models of cerebral I/R injury.
- Assessed miR-7-5p and Sirtuin 1 (sirt1) expression levels using RT-qPCR.
- Utilized luciferase reporter assays to confirm sirt1 as a direct target of miR-7-5p.
- Performed rescue experiments with sirt1 overexpression to validate the regulatory pathway.
Main Results:
- miR-7-5p expression was significantly upregulated in both in vivo and in vitro cerebral I/R models.
- Inhibition of miR-7-5p attenuated cerebral injury, inflammation, and neuronal apoptosis.
- Sirt1 was identified as a direct target of miR-7-5p, with its expression downregulated in I/R conditions.
- miR-7-5p negatively regulated sirt1 expression, and sirt1 overexpression reversed the detrimental effects of miR-7-5p upregulation on I/R injury.
Conclusions:
- miR-7-5p exacerbates cerebral I/R injury by targeting and downregulating sirt1.
- Targeting the miR-7-5p/sirt1 axis presents a novel therapeutic strategy for mitigating cerebral I/R injury.
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