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与 FOXO3 相关的 microRNAs 在细胞衰老和其他应激反应中的作用。

MicroRNAs-associated with FOXO3 in cellular senescence and other stress responses.

机构信息

Department of Pharmacology, Faculty of Medicine, Universiti Malaya, 50603, Wilayah Persekutuan Kuala Lumpur, Malaysia.

出版信息

Biogerontology. 2024 Feb;25(1):23-51. doi: 10.1007/s10522-023-10059-6. Epub 2023 Aug 30.

Abstract

FOXO3 is a member of the FOXO transcription factor family and is known for regulating cellular survival in response to stress caused by various external and biological stimuli. FOXO3 decides cell fate by modulating cellular senescence, apoptosis and autophagy by transcriptional regulation of genes involved in DNA damage response and oxidative stress resistance. These cellular processes are tightly regulated physiologically, with FOXO3 acting as the hub that integrates signalling networks controlling them. The activity of FOXO3 is influenced by post-translational modifications, altering its subcellular localisation. In addition, FOXO3 can also be regulated directly or indirectly by microRNAs (miRNAs) or vice versa. This review discusses the involvement of various miRNAs in FOXO3-driven cellular responses such as senescence, apoptosis, autophagy, redox and inflammation defence. Given that these responses are linked and influence cell fate, a thorough understanding of the complex regulation by miRNAs would provide key information for developing therapeutic strategy and avoid unintended consequences caused by off-site targeting of FOXO3.

摘要

FOXO3 是 FOXO 转录因子家族的一员,其特征在于调节细胞存活,以响应各种外部和生物刺激引起的应激。FOXO3 通过转录调节参与 DNA 损伤反应和氧化应激抗性的基因来调节细胞衰老、凋亡和自噬,从而决定细胞命运。这些细胞过程在生理上受到严格调控,FOXO3 作为整合控制它们的信号网络的枢纽发挥作用。FOXO3 的活性受翻译后修饰的影响,改变其亚细胞定位。此外,FOXO3 还可以直接或间接受到 microRNAs(miRNAs)的调节,反之亦然。本综述讨论了各种 miRNAs 在 FOXO3 驱动的细胞反应中的作用,如衰老、凋亡、自噬、氧化还原和炎症防御。鉴于这些反应是相互关联的,并影响细胞命运,对 miRNA 进行复杂调节的深入了解将为开发治疗策略提供关键信息,并避免因 FOXO3 的脱靶而产生意外后果。

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