Sport and Health College of Guangxi Normal University, Guilin, China.
Department of Neurosurgery, Affiliated Hospital of Guilin Medical University, No.15 Lequn Road, Xiufeng District, Guilin, China.
Metab Brain Dis. 2022 Dec;37(8):2915-2924. doi: 10.1007/s11011-022-01051-z. Epub 2022 Aug 12.
Alzheimer's disease (AD) is a high incidence neurodegenerative disease. Emerging evidence suggests that circular RNAs (circRNAs) play an important modulator in the pathogenesis of AD. The aim of this paper was to reconnoiter the effects of circular RNA_0003611 (circ_0003611) on Aβ-triggered neuronal injury in AD. In this work, the abundance of circ_0003611 was augmented in AD patients and SH-SY5Y and SK-N-SH cells treated with Aβ. Aβ-mediated cell proliferation, apoptosis, inflammatory response, oxidative stress, and glycolysis were abolished through circ_0003611 silencing. Circ_0003611 worked as a miR-383-5p sponge, and the protective role of circ_0003611 absence on Aβ-triggered neuronal injury was overturned by releasing miR-383-5p. Meanwhile, miR-383-5p directly targeted KIF1B, and miR-383-5p upregulation might relieve Aβ-triggered neuronal injury by reducing KIF1B expression. Mechanical analysis discovered that circ_0003611 served as a sponge of miR-383-5p to impact KIF1B expression. These findings indicated that circ_0003611 improved Aβ-triggered neuronal injury in AD through targeting the miR-383-5p/KIF1B axis, which might deliver innovative therapy targeting for AD.
阿尔茨海默病（AD）是一种高发病率的神经退行性疾病。新出现的证据表明，环状 RNA（circRNA）在 AD 的发病机制中起着重要的调节作用。本文旨在探讨环状 RNA_0003611（circ_0003611）对 AD 中 Aβ 触发的神经元损伤的影响。在这项工作中，AD 患者和 Aβ 处理的 SH-SY5Y 和 SK-N-SH 细胞中 circ_0003611 的丰度增加。通过沉默 circ_0003611，抑制了 Aβ 介导的细胞增殖、凋亡、炎症反应、氧化应激和糖酵解。Circ_0003611 作为 miR-383-5p 的海绵，circ_0003611 缺失对 Aβ 触发的神经元损伤的保护作用被释放 miR-383-5p 所推翻。同时，miR-383-5p 直接靶向 KIF1B，上调 miR-383-5p 可能通过减少 KIF1B 表达来缓解 Aβ 触发的神经元损伤。力学分析发现 circ_0003611 作为 miR-383-5p 的海绵来影响 KIF1B 的表达。这些发现表明，circ_0003611 通过靶向 miR-383-5p/KIF1B 轴改善 AD 中 Aβ 触发的神经元损伤，这可能为 AD 提供创新的治疗靶点。
