miR-6076 通过靶向 BCL6 调节 SH-SY5Y 细胞中淀粉样β诱导的神经元损伤。

miR-6076 targets BCL6 in SH-SY5Y cells to regulate amyloid-β-induced neuronal damage.

机构信息

Department of Human Anatomy, Institute of Neurobiology, Nantong University, Nantong, Jiangsu, PR China.

Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, PR China.

出版信息

J Cell Mol Med. 2023 Dec;27(24):4145-4154. doi: 10.1111/jcmm.17999. Epub 2023 Oct 17.

Amyloid-β (Aβ ) is strongly associated with Alzheimer's disease (AD). The aim of this study is to elucidate whether and how miR-6076 participates in the modulation of amyloid-β (Aβ)-induced neuronal damage. To construct the neuronal damage model, SH-SY5Y cells were treated with Aβ . By qRT-PCR, we found that miR-6076 is significantly upregulated in Aβ -treated SH-SY5Y cells. After miR-6076 inhibition, p-Tau and apoptosis levels were downregulated, and cell viability was increased. Through online bioinformatics analysis, we found that B-cell lymphoma 6 (BCL6) was a directly target of miR-6076 via dual-luciferase reporter assay. BCL6 overexpression mediated the decrease in elevated p-Tau levels and increased viability in SH-SY5Y cells following Aβ1-42 treatment. Our results suggest that down-regulation of miR-6076 could attenuate Aβ -induced neuronal damage by targeting BCL6, which provided a possible target to pursue for prevention and treatment of Aβ-induced neuronal damage in AD.

淀粉样蛋白-β（Aβ）与阿尔茨海默病（AD）密切相关。本研究旨在阐明 miR-6076 是否以及如何参与调节淀粉样蛋白-β（Aβ）诱导的神经元损伤。为构建神经元损伤模型，用 Aβ处理 SH-SY5Y 细胞。通过 qRT-PCR，我们发现 miR-6076 在 Aβ处理的 SH-SY5Y 细胞中显著上调。抑制 miR-6076 后，p-Tau 和细胞凋亡水平下调，细胞活力增加。通过在线生物信息学分析，我们发现 B 细胞淋巴瘤 6（BCL6）通过双荧光素酶报告基因检测是 miR-6076 的直接靶标。BCL6 的过表达介导了 Aβ1-42 处理后 SH-SY5Y 细胞中 p-Tau 水平升高和活力增加的减少。我们的结果表明，下调 miR-6076 通过靶向 BCL6 可以减轻 Aβ诱导的神经元损伤，为预防和治疗 AD 中 Aβ 诱导的神经元损伤提供了一个可能的靶点。