circFoxO3 的沉默通过调节线粒体凋亡通路保护 HT22 细胞免受谷氨酸诱导的氧化损伤。
Silencing of circFoxO3 Protects HT22 Cells from Glutamate-Induced Oxidative Injury via Regulating the Mitochondrial Apoptosis Pathway.
机构信息
Department of Emergency, The Second Affiliated Hospital of Guangzhou Medical University, 250 Changgang East Road, Guangzhou, Guangdong, 510260, People's Republic of China.
Department of Geriatrics, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China.
出版信息
Cell Mol Neurobiol. 2020 Oct;40(7):1231-1242. doi: 10.1007/s10571-020-00817-2. Epub 2020 Mar 5.
Abstract
Recent studies demonstrated that FoxO3 circular RNA (circFoxO3) plays an important regulatory role in tumourigenesis and cardiomyopathy. However, the role of circFoxO3 in neurodegenerative diseases remains unknown. The aim of this study was to examine the possible role of circFoxO3 in neurodegenerative diseases and the underlying mechanisms. To model human neurodegenerative conditions, hippocampus-derived neurons were treated with glutamate. Using molecular and cellular biology approaches, we found that circFoxO3 expression was significantly higher in the glutamate treatment group than that in the control group. Furthermore, silencing of circFoxO3 protected HT22 cells from glutamate-induced oxidative injury through the inhibition of the mitochondrial apoptotic pathway. Collectively, our study demonstrates that endogenous circFoxO3 plays a key role in inducing apoptosis and neuronal cell death and may act as a novel therapeutic target for neurodegenerative diseases.
摘要
最近的研究表明，FoxO3 环状 RNA（circFoxO3）在肿瘤发生和心肌病中发挥着重要的调节作用。然而，circFoxO3 在神经退行性疾病中的作用尚不清楚。本研究旨在探讨 circFoxO3 在神经退行性疾病中的可能作用及其潜在机制。为了模拟人类神经退行性疾病的情况，我们用谷氨酸处理海马来源的神经元。通过分子和细胞生物学方法，我们发现谷氨酸处理组中 circFoxO3 的表达明显高于对照组。此外，circFoxO3 的沉默通过抑制线粒体凋亡途径来保护 HT22 细胞免受谷氨酸诱导的氧化损伤。综上所述，我们的研究表明内源性 circFoxO3 在诱导细胞凋亡和神经元死亡中起着关键作用，可能成为神经退行性疾病的新治疗靶点。
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2
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Mol Cancer. 2019 Sep 3;18(1):133. doi: 10.1186/s12943-019-1060-9.
3
Circular RNAs: Biogenesis, Mechanism, and Function in Human Cancers.环状 RNA：在人类癌症中的生物发生、机制和功能。
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5
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9
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