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调节卵巢癌细胞细胞微环境的外泌体微小RNA的动态与功能分析

Dynamic and functional analyses of exosomal miRNAs regulating cellular microenvironment of ovarian cancer cells.

作者信息

Wang Zhaoxia, Huang Yanan, He Simin, Zhou Ying, Zhao Le, Wang Fuyuan

机构信息

Department of Gynecology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China.

First Hospital of Shanxi Medical University, 85 South Jiefang Road, Taiyuan, Shanxi, 030001, P.R. China.

出版信息

J Ovarian Res. 2025 Feb 10;18(1):25. doi: 10.1186/s13048-025-01608-3.

DOI:10.1186/s13048-025-01608-3
PMID:39930447
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11808964/
Abstract

BACKGROUND

Exosomes, extracellular vesicles with an average diameter of 30 ~ 150 nm, are pivotal in mediating the cellular microenvironment (CM) through their cargo-carrying capability. Despite extensive studies, the dynamic and regulatory mechanisms of exosomal cargoes, including lipids, proteins, nucleic acids, and metabolites, remain poorly understood.

METHODS

In this study, we collected culture medium of ovarian cancer cells at four different time points (12, 24, 36, 48 h). Exosomes were isolated using ultracentrifugation, and miRNA sequencing was performed for exosomes from each group (T12, T24, T36, and T48).

RESULTS

A total of 131 miRNAs were identified in all groups. Specifically, 41, 115, 63, and 24 miRNAs were detected in the T12, T24, T36, and T48 groups, respectively. Among these, 15 miRNAs were common to the all groups, while 3, 57, 10, and 3 miRNAs were unique to the T12, T24, T36, and T48 groups, respectively. Functional analyses of the target genes for both common and specific miRNAs indicated that numerous target genes were involved in signaling pathways and cancer-related processes.

CONCLUSION

It suggested that exosomal miRNAs might be critical in intercellular communication and in dynamically remodeling the tumor microenvironment. These insights could enhance our understanding of the role of exosomal miRNAs in cancer biology and inform the development of novel therapeutic strategies.

摘要

背景

外泌体是平均直径为30至150纳米的细胞外囊泡,通过其携带货物的能力在介导细胞微环境(CM)中起关键作用。尽管进行了广泛的研究,但外泌体货物(包括脂质、蛋白质、核酸和代谢物)的动态和调节机制仍知之甚少。

方法

在本研究中,我们在四个不同时间点(12、24、36、48小时)收集卵巢癌细胞的培养基。使用超速离心法分离外泌体,并对每组(T12、T24、T36和T48)的外泌体进行miRNA测序。

结果

所有组共鉴定出131种miRNA。具体而言,在T12、T24、T36和T48组中分别检测到41、115、63和24种miRNA。其中,15种miRNA在所有组中都有,而3、57、10和3种miRNA分别是T12、T24、T36和T48组特有的。对常见和特定miRNA的靶基因进行功能分析表明,许多靶基因参与信号通路和癌症相关过程。

结论

这表明外泌体miRNA可能在细胞间通讯和动态重塑肿瘤微环境中起关键作用。这些见解可以增强我们对外泌体miRNA在癌症生物学中的作用的理解,并为新型治疗策略的开发提供信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea9b/11808964/9bf28994e138/13048_2025_1608_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea9b/11808964/86a51352ea3d/13048_2025_1608_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea9b/11808964/7af6b3ff3825/13048_2025_1608_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea9b/11808964/d1ee2a0f31fb/13048_2025_1608_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea9b/11808964/ba11534a312c/13048_2025_1608_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea9b/11808964/9bf28994e138/13048_2025_1608_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea9b/11808964/86a51352ea3d/13048_2025_1608_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea9b/11808964/7af6b3ff3825/13048_2025_1608_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea9b/11808964/d1ee2a0f31fb/13048_2025_1608_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea9b/11808964/ba11534a312c/13048_2025_1608_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea9b/11808964/9bf28994e138/13048_2025_1608_Fig5_HTML.jpg

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本文引用的文献

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Comparative analyses of salivary exosomal miRNAs for patients with or without lung cancer.肺癌患者与非肺癌患者唾液外泌体微小RNA的比较分析。
Front Genet. 2023 Nov 3;14:1249678. doi: 10.3389/fgene.2023.1249678. eCollection 2023.
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Exosomal miRNAs in the microenvironment of pancreatic cancer.外泌体 miRNAs 在胰腺癌微环境中的作用。
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Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer.外泌体的生物发生:在癌症中的机制、调控和治疗意义。
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Molecular Biomarkers for the Early Detection of Ovarian Cancer.用于卵巢癌早期检测的分子生物标志物。
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Emerging role of exosomes in cancer progression and tumor microenvironment remodeling.外泌体在癌症进展和肿瘤微环境重塑中的新兴作用。
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Role of exosomal non-coding RNAs from tumor cells and tumor-associated macrophages in the tumor microenvironment.肿瘤细胞和肿瘤相关巨噬细胞来源的外泌体非编码 RNA 在肿瘤微环境中的作用。
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