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Πέμπτη 1 Απριλίου 2021

Knockdown of lncRNA TTTY15 alleviates ischemia/reperfusion-induced inflammation and apoptosis of PC12 cells by targeting miR-766-5p

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Exp Ther Med. 2021 May;21(5):511. doi: 10.3892/etm.2021.9942. Epub 2021 Mar 19.

ABSTRACT

The pathogenesis of ischemic stroke is extremely complex and has a significant impact on the quality of life of the patients. Accumulating studies have reported that long non-coding RNAs (lncRNAs) may be associated with the progression of ischemic stroke. However, the role and underlying mechanism of action of the lncRNA testis-specific transcript Y-linked 15 (TTTY15) in ischemic stroke remains unknown. The present study analyzed the expression levels of TTTY15 in PC12 cells injured by oxygen-glucose deprivation/reperfusion (OGD/R). The effects of the knockdown of TTTY15 expression on the levels of the inflammatory cytokines TNF-α, IL-1β, IL-18 and IL-10, cell apoptosis and the expression levels of the apoptosis-associated proteins Bcl-2, Bax, cleaved caspase-3, caspase-3, cleaved caspase-9 and caspase-9, were subsequently analyzed in OGD/R-treat ed PC12 cells using ELISA, flow cytometry and western blotting, respectively. In addition, the downstream target gene of TTTY15 was verified using a dual luciferase reporter assay. The effects of TTTY15 on the inflammation and apoptosis of PC12 cells treated with OGD/R were determined by targeting miR-766-5p. The results of the present study revealed that TTTY15 expression was upregulated in OGD/R-treated PC12 cells. The knockdown of TTTY15 significantly decreased the concentrations of the proinflammatory factors TNF-α, IL-1β and IL-18, while it increased the concentration of the anti-inflammatory cytokine IL-10 in OGD/R-treated PC12 cells. Apoptosis was also suppressed following gene silencing of TTTY15. Subsequently, miR-766-5p was identified as a target gene of TTTY15 using a dual luciferase reporter assay and the expression levels of TTTY15 and miR-766-5p were found to be negatively correlated. The overexpression of miR-766-5p alleviated the stimulatory effect of TTTY15 overex pression on the inflammation and apoptosis of PC12 cells treated with OGD/R. Therefore, the present study revealed that TTTY15 knockdown improved the OGD/R-induced injury of PC12 cells by upregulating miR-766-5p expression.

PMID:33791020 | PMC:PMC8005683 | DOI:10.3892/etm.2021.9942

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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