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miR-548az-5p通过调控分娩时KATNAL1的表达诱导羊膜上皮细胞衰老。

miR-548az-5p induces amniotic epithelial cell senescence by regulating KATNAL1 expression in labor.

作者信息

Jing Die, Liu Qian, Zhang Hongyuan, Li Yuchen, Jiang Xiaotong, Cai Yanjun, Wang Xietong, Li Lei

机构信息

Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.

The Laboratory of Medical Science and Technology Innovation Center (Institute of Translational Medicine), Shandong First Medical University (Shandong Academy of Medical Sciences) of China, Jinan, 250117, Shandong, China.

出版信息

Sci Rep. 2024 Dec 5;14(1):30380. doi: 10.1038/s41598-024-82390-y.

Abstract

Amniotic fluid exosomes (AF-Exos) from term labor (TL) cause amniotic membrane senescence and induce labor. However, the intrinsic mechanism through which this occurs remains unknown. Therefore, we performed microRNA (miRNA) microarray chip screening of AF-Exos obtained from TL and terms not in labor and discovered that the expression of miR-548az-5p was significantly upregulated in TL. This study aimed to explore the role of miR-548az-5p in AF-Exos-induced human amniotic epithelial cells (hAECs) senescence for labor initiation. Bioinformatics analysis revealed that Katanin catalytic subunit A1 like 1 (KATNAL1) is a potential miR-548az-5p target. In hAECs, the upregulation of miR-548az-5p suppressed KATNAL1 expression, disorganized microtubules, increased senescence-associated secretory phenotype-related biomarkers, and inhibited cell proliferation by cyclin D1 and cyclin-dependent kinase 6 (CDK6). This study identified that miR-548az-5p is involved in the senescence of amniotic epithelial cells by targeting KATNAL1 to induce labor. Notably, this study offers new perspectives on the mediation of cellular senescence using AF-Exos miRNAs, which results in labor.

摘要

足月分娩(TL)时的羊水外泌体(AF-Exos)可导致羊膜衰老并引发分娩。然而,其发生的内在机制尚不清楚。因此,我们对来自足月分娩和未分娩足月孕妇的AF-Exos进行了微小RNA(miRNA)微阵列芯片筛选,发现miR-548az-5p在足月分娩时的表达显著上调。本研究旨在探讨miR-548az-5p在AF-Exos诱导人羊膜上皮细胞(hAECs)衰老以启动分娩中的作用。生物信息学分析显示,katanin催化亚基A1样1(KATNAL1)是miR-548az-5p的潜在靶标。在hAECs中,miR-548az-5p的上调抑制了KATNAL1的表达,破坏了微管结构,增加了衰老相关分泌表型相关生物标志物,并通过细胞周期蛋白D1和细胞周期蛋白依赖性激酶6(CDK6)抑制细胞增殖。本研究确定miR-548az-5p通过靶向KATNAL1诱导分娩,参与了羊膜上皮细胞的衰老。值得注意的是,本研究为利用AF-Exos miRNAs介导细胞衰老导致分娩提供了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81c8/11621115/e4c563e81cff/41598_2024_82390_Fig1_HTML.jpg

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