MiR‐370 accelerated cerebral ischemia reperfusion injury via targeting SIRT6 and regulating Nrf2/ARE signal pathway

Autor: Zhong‐Fan Ruan, Ming Xie, Shu‐Jia Gui, Fang Lan, Juan Wan, Yan Li
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Kaohsiung Journal of Medical Sciences, Vol 36, Iss 9, Pp 741-749 (2020)
Druh dokumentu: article
ISSN: 2410-8650
1607-551X
DOI: 10.1002/kjm2.12219
Popis: Abstract Cerebral ischemia reperfusion (CIR) is one of the highly lethal diseases in the world. MicroRNA‐370 (miR‐370) exerts multiple functions in different diseases. However, further research is needed to investigate the potential role of miR‐370 in CIR injury. The in vivo middle cerebral artery occlusion (MCAO) rat model and in vitro oxygen‐glucose deprivation/reoxygenation (OGD/R) SH‐SY5Y cell model were successfully established to mimic CIR injury. The infarct sizes of brain tissues from rats were evaluated. The relationship between miR‐370 and silencing information regulatory protein 6 (SIRT6) was confirmed by luciferase activity assay. The cell viability and apoptosis were determined by CCK‐8 assay and terminal‐deoxynucleoitidyl transferase mediated nick end labeling staining. In this study, miR‐370 was upregulated in brain tissues of MCAO rats and knockdown of miR‐370 decreased cerebral infarction volume of MCAO rats and it alleviated CIR injury in vivo. The in vitro experiments indicated that knockdown of miR‐370 promoted cell viability and alleviated OGD/R‐induced SH‐SY5Y cell apoptosis. Additionally, the TargetScan predicted that SIRT6 was a target of miR‐370 and confirmed by luciferase activity assay. Moreover, miR‐370 inhibited SIRT6 expression and regulated Nrf2/ARE signal pathway, whereas overexpression of SIRT6 partly reversed the effect of miR‐370 on OGD/R‐induced SH‐SY5Y cell injury. Thus, we could conclude that miR‐370 accelerated CIR injury via targeting SIRT6 and regulating Nrf2/ARE signal pathway, which might provide novel therapeutic targets for CIR injury treatment.
Databáze: Directory of Open Access Journals
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