MiR-155-5p accelerates cerebral ischemia-reperfusion injury via targeting DUSP14 by regulating NF-κB and MAPKs signaling pathways

Y Shi, K Li, K Xu, Q-H Liu
European Review for Medical and Pharmacological Sciences 2020, 24 (3): 1408-1419

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.

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