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

IF 2.4 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Biotechnology Pub Date : 2024-10-14 DOI:10.1007/s12033-024-01298-0
Yihong Guo, Lujing Chen, Qiulin Ma, Peiyu Liu
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引用次数: 0

摘要

复发性自然流产(RSA)是一种妊娠疾病,滋养细胞参与了其复杂的发病机制。本研究旨在确定外泌体miR-494在促进不明原因自然流产(uRSA)发展中的功能作用。研究人员采集了15例uRSA组织和15例健康对照组,以比较外泌体miR-494的表达。采用超速离心法分离血清外泌体,并用透射电子显微镜(TEM)检查外泌体的特征。通过CCK-8、EdU、伤口愈合和Transwell试验测定了外泌体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高表达的外泌体处理HTR-8/SVneo细胞,可降低其活力、侵袭和迁移。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。外泌体miR-494和mTOR是uRSA患者潜在的预测性生物标志物和治疗靶标。
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Exosomal miR-494 Regulates the Biological Behavior of Trophoblasts by Targeting mTOR in Unexplained Recurrent Spontaneous Abortion.

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.

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来源期刊
Molecular Biotechnology
Molecular Biotechnology 医学-生化与分子生物学
CiteScore
4.10
自引率
3.80%
发文量
165
审稿时长
6 months
期刊介绍: Molecular Biotechnology publishes original research papers on the application of molecular biology to both basic and applied research in the field of biotechnology. Particular areas of interest include the following: stability and expression of cloned gene products, cell transformation, gene cloning systems and the production of recombinant proteins, protein purification and analysis, transgenic species, developmental biology, mutation analysis, the applications of DNA fingerprinting, RNA interference, and PCR technology, microarray technology, proteomics, mass spectrometry, bioinformatics, plant molecular biology, microbial genetics, gene probes and the diagnosis of disease, pharmaceutical and health care products, therapeutic agents, vaccines, gene targeting, gene therapy, stem cell technology and tissue engineering, antisense technology, protein engineering and enzyme technology, monoclonal antibodies, glycobiology and glycomics, and agricultural biotechnology.
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