MicroRNA Let-7i Is a Promising Serum Biomarker for Post-stroke Cognitive Impairment and Alleviated OGD-Induced Cell Damage in vitro by Regulating Bcl-2.

Zhan-Qiang Wang,Kuo Li,Tian-Tian Huo,Pei-Yuan Lv,Jie Huang

doi:10.3389/fnins.2020.00215

Abstract

BackgroundThe mechanism of post-stroke cognitive impairment (PSCI) has not been explained. We aimed to investigate whether miR-let-7i participates in the PSCI and illuminates its underlying role in oxygen–glucose deprivation (OGD)-induced cell apoptosis.MethodsBlood samples from 36 subjects with PSCI and 38 with post-stroke cognitive normality (Non-PSCI) were collected to evaluate the differential expression of miR-let-7 family members, using qRT-PCT analysis. Spearman correlation was performed to estimate the correlation between the miR-1et-7i level and Montreal Cognitive Assessment (MoCA) score. Treatment of SH-SY5Y cells with OGD was used to induce cell apoptosis in vitro. Effects of miR-let-7i on OGD-induced cell apoptosis was estimated after transfection. The target gene of miR-let-7i was analyzed by dual luciferase reporter gene assay.ResultsThe expression of miR-let-7i was up-regulated in PSCI patients compared with Non-PSCI (p < 0.001) and negatively correlated with MoCA score (r = −0.643, p < 0.001). When exposed to OGD, SH-SY5Y cells showed significant apoptosis accompanied by miR-let-7i up-regulation. In OGD-treated cells, miR-let-7i up-regulation was accompanied by cell apoptosis, while down-regulation showed the opposite effect. Luciferase reporter assay showed that Bcl-2 was a target gene of miR-let-7i. Western blot showed that miR-let-7i up-regulation promoted Bcl-2 expression, while qRT-PCR showed that miR-let-7i had no effect on Bcl-2 expression.ConclusionmiR-let-7i was overexpressed in PSCI patients and it could be used as a diagnostic biomarker for PSCI. We illuminated the potential mechanism that miR-let-7i alleviated OGD-induced cell damage by targeting Bcl-2 at the post-transcriptional level.

Highlights

Stroke is a major cause of cognitive impairment and dementia and has been reported to increase the risk of cognitive impairment at least five to eight times (Merino, 2002; Srikanth et al, 2003; Qu et al, 2015)
The inclusion criteria of poststroke cognitive impairment (PSCI) group were as follows: (1) the subjects had a history of stroke and/or neuroimaging (CT or MRI) provided evidence of cerebrovascular disease; (2) cognitive impairment was judged to have a vascular cause, and a Montreal Cognitive Assessment (MoCA) score
To explore the potential biomarkers in the miR-let-7 family for patients with PSCI, blood samples were collected from 38 patients with Non-PSCI and 36 patients with PSCI to detect the miRNA expression level

Summary

Introduction

Stroke is a major cause of cognitive impairment and dementia and has been reported to increase the risk of cognitive impairment at least five to eight times (Merino, 2002; Srikanth et al, 2003; Qu et al, 2015). The prevalence of poststroke cognitive impairment (PSCI) is increasing because of the aging population and a rise in the number of stroke survivors (Jacquin et al, 2014). PSCI occur immediately after a stroke or after a certain period, but it is often overlooked at onset (Chi et al, 2019). The timely diagnosis and prevention of PSCI are critical at present. The pathogenesis of PSCI has been shown that due to the paucity of energy or oxygen to the brain, the region-specific neural damage occurred, leading to a progressive cognitive impairment (Wahul et al, 2018). The mechanism of post-stroke cognitive impairment (PSCI) has not been explained. We aimed to investigate whether miR-let-7i participates in the PSCI and illuminates its underlying role in oxygen–glucose deprivation (OGD)-induced cell apoptosis

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