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miR-23a-3p 通过靶向 FOXO3a 在人类衰老过程中的作用。

The Role of microRNA-23a-3p in the Progression of Human Aging Process by Targeting FOXO3a.

机构信息

Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.

出版信息

Mol Biotechnol. 2024 Feb;66(2):277-287. doi: 10.1007/s12033-023-00746-7. Epub 2023 Apr 23.

Abstract

Aging results in deterioration of body functions and, ultimately, death. miRNAs contribute to the regulation of aging. The aim of this study was to explore the contribution of miRNAs to aging and senescence-related changes in gene expression. The expression changes of miRNAs in the blood of people and animal samples collected from different age subjects were examined using Affymetrix miRNA 4.0 microarray and qRT-PCR. MTT assay and flow cytometry were used to examine the effect of miR-23a on cell functions in WI-38 cells. The expression levels of 48 miRNAs, including miR-23a, miR-21, and miR-100, in the blood samples were higher in the middle-aged group than in the young or elderly group. Animal studies further suggested that the expression of miR-23a increased with age. In addition, upregulation of miR-23a dramatically suppressed the cell proliferation and arrested the WI-38 cell cycle in vitro. FOXO3a has been identified as a target gene of miR-23a. MiR-23a downregulated the expression of FOXO3a in WI-38 cells. MiRNAs have different expression levels in different age groups. miR-23a could suppress cell proliferation and arrest the cell cycle in WI-38 cells, which elucidated the mechanism through which miR-23a exerts pivotal role in WI-38 cells by targeting FOXO3a.

摘要

衰老是身体机能的恶化,最终导致死亡。miRNAs 有助于调节衰老。本研究旨在探讨 miRNAs 对衰老和与衰老相关的基因表达变化的贡献。使用 Affymetrix miRNA 4.0 微阵列和 qRT-PCR 检测了来自不同年龄受试者的人血和动物样本中 miRNAs 的表达变化。MTT 测定和流式细胞术用于检测 miR-23a 对 WI-38 细胞功能的影响。血液样本中包括 miR-23a、miR-21 和 miR-100 在内的 48 种 miRNAs 的表达水平在中年组中高于年轻组或老年组。动物研究进一步表明,miR-23a 的表达随年龄增长而增加。此外,miR-23a 的上调显著抑制了细胞增殖,并使 WI-38 细胞周期在体外停滞。FOXO3a 已被确定为 miR-23a 的靶基因。miR-23a 下调了 WI-38 细胞中 FOXO3a 的表达。miRNAs 在不同年龄组中的表达水平不同。miR-23a 可以抑制 WI-38 细胞的增殖并使细胞周期停滞,这阐明了 miR-23a 通过靶向 FOXO3a 对 WI-38 细胞发挥关键作用的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67c9/10803409/037b07ad1387/12033_2023_746_Fig1_HTML.jpg

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