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Δευτέρα 1 Νοεμβρίου 2021

MicroRNA-424 alleviates neurocyte injury by targeting PDCD4 in a cellular model of cerebral ischemic stroke

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Exp Ther Med. 2021 Dec;22(6):1453. doi: 10.3892/etm.2021.10888. Epub 2021 Oct 15.

ABSTRACT

Cerebral ischemic stroke is the primary cause of stroke-associated mortality and disability, and current therapeutic options are limited and ineffective. The present study aimed to investigate the potential of apoptotic therapy and the role of microRNA (miR)-424 in cerebral ischemic stroke. PC12 cells, a cloned cell line from rat adrenal pheochromocytoma, were treated with CoCl2 to construct a cellular ischemia model. mRNA and protein levels of programmed cell death protein 4 (PDCD4), Bcl-2, Bax, caspase-3, PI3K and AKT were evaluated using reverse transcription-quantitative PCR and western blot analyses, respectively. Cell Counting Kit-8 assays were performed to examine cell viability in the ischemia model. Flow cytometry was conducted to evaluate the apoptosis of ischemic cells. Furthermore, a luciferase assay was performed to verify the target gene of miR-424. It was revealed that the expression level of miR-424 was downregulated in the ischemia model, while the expression of PDCD4 was upregulated. Moreover, the expression of miR-424 was increased after treatment with miR-424 mimics. The mRNA and protein expression of PDCD4 was upregulated after transfection with pcDNA3.1-PDCD4. PDCD4 was predicted and demonstrated to be a target of miR-424. Notably, overexpression of miR-424 increased cell viability and inhibited apoptosis in the ischemia model, which was reversed by co-treatment with pcDNA3.1-PDCD4. Furthermore, overexpression of miR-424 regulated the expression of PDCD4, Bax, Bcl-2, phosphorylated-PI3K/AKT and caspase-3, which was restored after co-transfection with pcDNA3.1-PDCD4. Collectively, the results indicated that miR-424 regulated the progression of cerebral ischemic stroke in a cellular model by targeting PDCD4.

PMID:34721695 | PMC:PMC8549098 | DOI:10.3892/etm.2021.10888

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