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MicroRNA miR-212 regulates PDCD4 to attenuate Aβ25–35-induced neurotoxicity via PI3K/AKT signaling pathway in Alzheimer’s disease
Biotechnology Letters ( IF 2.7 ) Pub Date : 2020-05-30 , DOI: 10.1007/s10529-020-02915-z
Yanjun Wang 1 , Qing Chang 2
Affiliation  

Alzheimer’s disease (AD) is a progressive neurodegenerative disease in the elderly. MicroRNA (miRNA) miR-212-3p (miR-212) has been reported to dysregulated in many neurodegenerative diseases including AD. However, the mechanism and function of miR-212 in AD has not been reported. The levels of miR-212 and PDCD4 in AD patients and Aβ25–35-treated SH-SY5Y and IMR-32 cells were measured by qRT-PCR and/or Western blot. The putative target of miR-212 was predicted by DIANA tools online database and the interaction between miR-212 and PDCD4 was validated by dual luciferase reporter assay and RNA pull-down assay. The cell proliferation, cell apoptosis and the protein levels of Bcl-2, Bax, Cleaved caspase 3, p-PI3K, PI3K, p-ATK and ATK were measured by MTT assay, flow cytometry and Western blot. The level of miR-212 was apparently down-regulated, and the level of PDCD4 was significantly up-regulated in plasma from AD patients and Aβ25–35-treated SH-SY5Y and IMR-32 cells. Following a dual luciferase reporter assay verified the direct interaction between miR-212 and PDCD4. The RNA pull-down assay further validated this interaction. The functional experiment indicated that PDCD4 mitigated the promotion effects on cell viability, the apoptosis-inhibited protein Bcl-2, the ratio of p-PI3K/PI3K, p-ATK/ATK and the suppressive effects on cell apoptosis and the corresponding protein levels of Bax, Cleaved caspase 3 caused by miR-212 mimics. All the data in this study revealed that miR-212 modulated PDCD4 to regulate cell proliferation, apoptosis through PI3K/AKT signaling pathway in Aβ25–35-treated SH-SY5Y and IMR-32 cells, and this new regulatory network may provide a novel mechanism of AD.

中文翻译:

MicroRNA miR-212通过PI3K/AKT信号通路在阿尔茨海默病中调节PDCD4以减弱Aβ25-35诱导的神经毒性

阿尔茨海默病 (AD) 是一种老年人的进行性神经退行性疾病。据报道,MicroRNA (miRNA) miR-212-3p (miR-212) 在包括 AD 在内的许多神经退行性疾病中失调。然而,miR-212在AD中的机制和功能尚未见报道。通过 qRT-PCR 和/或蛋白质印迹测量 AD 患者和 Aβ25-35 处理的 SH-SY5Y 和 IMR-32 细胞中 miR-212 和 PDCD4 的水平。miR-212 的假定靶点由 DIANA 工具在线数据库预测,miR-212 和 PDCD4 之间的相互作用通过双荧光素酶报告基因测定和 RNA 下拉测定验证。采用MTT法、流式细胞术和Western blot检测细胞增殖、细胞凋亡和Bcl-2、Bax、Cleaved caspase 3、p-PI3K、PI3K、p-ATK和ATK的蛋白水平。miR-212 的水平明显下调,PDCD4 水平在 AD 患者和 Aβ25-35 处理的 SH-SY5Y 和 IMR-32 细胞的血浆中显着上调。在双荧光素酶报告基因检测之后,证实了 miR-212 和 PDCD4 之间的直接相互作用。RNA 下拉分析进一步验证了这种相互作用。功能实验表明,PDCD4减轻了对细胞活力、凋亡抑制蛋白Bcl-2、p-PI3K/PI3K、p-ATK/ATK比值的促进作用,以及对细胞凋亡和相应蛋白水平的抑制作用。 Bax,由 miR-212 模拟物引起的 Cleaved caspase 3。本研究中的所有数据表明,miR-212 通过 PI3K/AKT 信号通路在 Aβ25-35 处理的 SH-SY5Y 和 IMR-32 细胞中调节 PDCD4 来调节细胞增殖、凋亡,这种新的调控网络可能提供一种新的机制的广告。
更新日期:2020-05-30
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