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外泌体miR-494通过靶向mTOR调控不明原因复发性自然流产中滋养层细胞的生物学行为

Exosomal miR-494 Regulates the Biological Behavior of Trophoblasts by Targeting mTOR in Unexplained Recurrent Spontaneous Abortion.

作者信息

Guo Yihong, Chen Lujing, Ma Qiulin, Liu Peiyu

机构信息

Department of Reproductive Immunology, Dongguan Maternal and Child Health Care Hospital, No. 99, Zhenxing Road, Dongcheng District, Dongguan, 523120, Guangdong, China.

Department of Clinical Laboratory, Dongguan Maternal and Child Health Care Hospital, Dongguan, 523120, Guangdong, China.

出版信息

Mol Biotechnol. 2024 Oct 14. doi: 10.1007/s12033-024-01298-0.

DOI:10.1007/s12033-024-01298-0
PMID:39402429
Abstract

Recurrent spontaneous abortion (RSA) is a pregnancy disorder, and trophoblasts are involved in its complex pathogenesis. This study aimed to identify the functional role of exosomal miR-494 in promoting the development of unexplained RSA (uRSA). 15 uRSA tissues and 15 healthy controls were collected to compare the exosomal miR-494 expression. The ultracentrifugation method was used for serum exosome isolation, and exosome characteristics were examined using transmission electron microscopy (TEM). The affection of exosomal miR-494 on HTR-8/SVneo cells were determined by CCK-8, EdU, Wound healing, and Transwell assays. Our findings demonstrated that miR-494 levels were markedly lower in placental tissue and plasma exosomes from patients with uRSA than in normal pregnant women. Furthermore, treatment with miR-494-overexpressing exosomes reduced the viability, invasion, and migration of HTR-8/SVneo cells. In terms of regulation, exosomal miR-494 downregulated mTOR levels in HTR-8/SVneo cells. Mechanism research suggested that exosomal miR-494 reduces the viability, invasion, and migration of trophoblasts by targeting mTOR. Exosomal miR-494 and mTOR are potential predicative biomarkers and therapeutic targets for uRSA patients.

摘要

复发性自然流产(RSA)是一种妊娠疾病,滋养细胞参与其复杂的发病机制。本研究旨在确定外泌体miR-494在促进不明原因复发性自然流产(uRSA)发展中的功能作用。收集15例uRSA组织和15例健康对照,比较外泌体miR-494表达。采用超速离心法分离血清外泌体,并用透射电子显微镜(TEM)检测外泌体特征。通过CCK-8、EdU、伤口愈合和Transwell试验确定外泌体miR-494对HTR-8/SVneo细胞的影响。我们的研究结果表明,uRSA患者胎盘组织和血浆外泌体中的miR-494水平明显低于正常孕妇。此外,用miR-494过表达外泌体处理可降低HTR-8/SVneo细胞的活力、侵袭和迁移能力。在调控方面,外泌体miR-494下调了HTR-8/SVneo细胞中的mTOR水平。机制研究表明,外泌体miR-494通过靶向mTOR降低滋养细胞的活力、侵袭和迁移能力。外泌体miR-494和mTOR是uRSA患者潜在的预测生物标志物和治疗靶点。

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本文引用的文献

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microRNAs as A Biomarker to Predict Embryo Quality Assessment in In Vitro Fertilization.微小RNA作为预测体外受精胚胎质量评估的生物标志物
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LDHA deficiency inhibits trophoblast proliferation via the PI3K/AKT/FOXO1/CyclinD1 signaling pathway in unexplained recurrent spontaneous abortion.乳酸脱氢酶A(LDHA)缺乏通过PI3K/AKT/FOXO1/细胞周期蛋白D1信号通路抑制不明原因复发性自然流产中滋养细胞的增殖。
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Recent Advances in Exosomal miRNA Biosensing for Liquid Biopsy.外泌体 miRNA 生物传感在液体活检中的最新进展。
Molecules. 2022 Oct 22;27(21):7145. doi: 10.3390/molecules27217145.
8
Plasma Exosomal miR-199a-5p Derived from Preeclampsia with Severe Features Impairs Endothelial Cell Function via Targeting SIRT1.重度子痫前期患者血浆来源的外泌体miR-199a-5p通过靶向SIRT1损害内皮细胞功能。
Reprod Sci. 2022 Dec;29(12):3413-3424. doi: 10.1007/s43032-022-00977-0. Epub 2022 Sep 7.
9
Role of Exosomes in Immunotherapy of Hepatocellular Carcinoma.外泌体在肝细胞癌免疫治疗中的作用
Cancers (Basel). 2022 Aug 21;14(16):4036. doi: 10.3390/cancers14164036.
10
IGFBP7 enhances trophoblast invasion via IGF-1R/c-Jun signaling in unexplained recurrent spontaneous abortion.IGFBP7 通过 IGF-1R/c-Jun 信号通路增强不明原因复发性自然流产的滋养细胞侵袭。
Reproduction. 2022 Oct 10;164(5):231-241. doi: 10.1530/REP-21-0501. Print 2022 Nov 1.