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miR-153-3p 通过靶向 GPR55 抑制神经干细胞的分化和增殖。

miR-153-3p suppresses the differentiation and proliferation of neural stem cells via targeting GPR55.

机构信息

Department of Neurology, The Affiliated Yan’an Hospital of Kunming Medical University, Kunming 650051, Yunnan, China.

Department of Gastroenterology, The Affiliated Yan’an Hospital of Kunming Medical University, Kunming 650051, Yunnan, China.

出版信息

Aging (Albany NY). 2023 Aug 27;15(16):8518-8527. doi: 10.18632/aging.204002.

Abstract

Alzheimer's disease is the most frequent neurodegenerative disease and is characterized by progressive cognitive impairment and decline. NSCs (neural stem cells) serve as beneficial and promising adjuncts to treat Alzheimer's disease. This study aimed to determine the role of miR-153-3p expression in NSC differentiation and proliferation. We illustrated that miR-153-3p was decreased and GPR55 was upregulated during NSC differentiation. IL-1β can induce miR-153-3p expression. Luciferase reporter analysis noted that elevated expression of miR-153-3p significantly inhibited the luciferase value of the WT reporter plasmid but did not change the luciferase value of the mut reporter plasmid. Ectopic miR-153-3p expression suppressed GPR55 expression in NSCs and identified GPR55 as a direct target gene of miR-153-3p. Ectopic expression of miR-153-3p inhibited NSC growth and differentiation into astrocytes and neurons. Elevated expression of miR-153-3p induced the release of proinflammatory cytokines, such as TNF-α, IL-1β and IL-6, in NSCs. Furthermore, miR-153-3p inhibited NSC differentiation and proliferation by targeting GPR55 expression. These data suggested that miR-153-3p may act as a clinical target for the therapeutics of neurodegenerative diseases.

摘要

阿尔茨海默病是最常见的神经退行性疾病,其特征是进行性认知障碍和下降。神经干细胞(NSCs)作为治疗阿尔茨海默病的有益且有前途的辅助手段。本研究旨在确定 miR-153-3p 表达在 NSC 分化和增殖中的作用。我们表明,miR-153-3p 在 NSC 分化过程中减少,而 GPR55 上调。IL-1β 可以诱导 miR-153-3p 的表达。荧光素酶报告基因分析表明,miR-153-3p 的高表达显著抑制 WT 报告质粒的荧光素酶值,但不改变 mut 报告质粒的荧光素酶值。外源性 miR-153-3p 表达抑制 NSCs 中的 GPR55 表达,并确定 GPR55 是 miR-153-3p 的直接靶基因。外源性表达 miR-153-3p 抑制 NSC 生长并分化为星形胶质细胞和神经元。miR-153-3p 的高表达诱导 NSCs 中促炎细胞因子如 TNF-α、IL-1β 和 IL-6 的释放。此外,miR-153-3p 通过靶向 GPR55 表达抑制 NSC 分化和增殖。这些数据表明,miR-153-3p 可能作为神经退行性疾病治疗的临床靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f45/10497013/d43572652d9f/aging-15-204002-g001.jpg

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