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  • Title: miR-325-3p Protects Neurons from Oxygen-Glucose Deprivation and Reoxygenation Injury via Inhibition of RIP3.
    Author: Yi S, Zhang C, Li N, Fu Y, Li H, Zhang J.
    Journal: Dev Neurosci; 2020; 42(2-4):83-93. PubMed ID: 33130681.
    Abstract:
    OBJECTIVE: Recent reports have corroborated that micro-RNAs (miRs) are related to the pathological changes of cerebral ischemia-reperfusion (CIR) induced injury. This work aimed to unearth the role and potential mechanism of miR-325-3p in regulating neuronal survival in CIR injury. METHODS: To conduct this investigation, we established an in vitro model of CIR injury by subjecting neurons to oxygen-glucose deprivation and reoxygenation (OGD/R). Gain and loss of function of miR-325-3p and receptor-interacting serine-threonine kinase 3 (RIP3) in neurons were performed to observe its effect on cell apoptosis and the release of lactate dehydrogenase. The levels of miR-325-3p and RIP3 in neurons were detected by qRT-PCR. Western blot was employed to inspect the levels of caspase3, Bax, and Bcl-2, as well as p38 and JNK phosphorylation. The relationship between miR-325-3p and RIP3 was detected by TargetScan and validated by dual-luciferase reporter assay. RESULTS: Firstly, miR-325-3p expression was obviously downregulated while RIP3 expression was upregulated in neurons following OGD/R treatment. Overexpressed miR-325-3p or downexpressed RIP3 ameliorated OGD/R-induced neuronal injury. Besides, RIP3 was a direct target mRNA of miR-325-3p. Additionally, Western blot revealed the mitogen-activated protein kinase (MAPK) pathway was involved in the regulation of miR-325-3p on OGD/R-induced neuronal injury. Furthermore, miR-325-3p was verified to hinder OGD/R-induced neuronal injury through downregulating RIP3. CONCLUSION: This study demonstrated that miR-325-3p targets RIP3 to inactivate the MAPK pathway, thereby protecting neurons against OGD/R-induced injury.
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