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工程化外泌体可恢复子宫体子宫内膜癌中miR-508-5p的表达,并通过靶向DLL3减少肿瘤进展和转移。

Engineered exosomes restore miR-508-5p expression in uterine corpus endometrial carcinoma and reduce tumor progression and metastasis by targeting DLL3.

作者信息

Li Yue-Ying, Liu Hui, Feng Jia-Lu, Tian Wen-Yan, Du Juan, Zhang Li-Ping

机构信息

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China.

Tianjin Key Laboratory of Female Reproductive Health and Eugenic, Tianjin Medical University General Hospital, Tianjin, China.

出版信息

Front Oncol. 2025 Feb 24;15:1532564. doi: 10.3389/fonc.2025.1532564. eCollection 2025.

DOI:10.3389/fonc.2025.1532564
PMID:40066092
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11891050/
Abstract

INTRODUCTION

Endometrial cancer (EC) is a growing global health concern. Understanding the molecular mechanisms driving EC is crucial for developing effective diagnostic and therapeutic strategies. This study investigates the roles of DLL3 and miR-508-5p in EC progression and explores a therapeutic approach using engineered exosomes to modulate their expression.

METHODS

TCGA data were analyzed, and experiments were performed to assess DLL3 and miR-508-5p function, and bioinformatics was used to confirm their interaction. Mesenchymal stem cells (MSCs) were engineered to produce miR-508-5p-overexpressing exosomes, and their therapeutic effects were tested in mouse models.

RESULTS

Elevated DLL3 and downregulated miR-508-5p were observed in EC and correlated with poor outcomes. miR-508-5p directly targets DLL3. Engineered exosomes restored miR-508-5p, inhibited DLL3, and reduced tumor growth and metastasis in mouse models.

DISCUSSION

The findings highlight the roles of DLL3 and miR-508-5p in EC. Targeting the miR-508-5p/DLL3 axis via exosome-mediated delivery represents a promising therapeutic strategy for EC.

摘要

引言

子宫内膜癌(EC)是一个日益引起全球健康关注的问题。了解驱动EC的分子机制对于制定有效的诊断和治疗策略至关重要。本研究调查了DLL3和miR-508-5p在EC进展中的作用,并探索了一种使用工程化外泌体调节其表达的治疗方法。

方法

分析了TCGA数据,并进行实验评估DLL3和miR-508-5p的功能,还利用生物信息学证实它们的相互作用。对间充质干细胞(MSC)进行工程改造以产生过表达miR-508-5p的外泌体,并在小鼠模型中测试其治疗效果。

结果

在EC中观察到DLL3升高和miR-508-5p下调,且与不良预后相关。miR-508-5p直接靶向DLL3。工程化外泌体恢复了miR-508-5p,抑制了DLL3,并减少了小鼠模型中的肿瘤生长和转移。

讨论

这些发现突出了DLL3和miR-508-5p在EC中的作用。通过外泌体介导的递送靶向miR-508-5p/DLL3轴代表了一种有前景的EC治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f738/11891050/5d7099297965/fonc-15-1532564-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f738/11891050/a724b966029e/fonc-15-1532564-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f738/11891050/57ff6b72f7b2/fonc-15-1532564-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f738/11891050/54769ac384bb/fonc-15-1532564-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f738/11891050/e56c459fc34e/fonc-15-1532564-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f738/11891050/b9a5d5363a84/fonc-15-1532564-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f738/11891050/5d7099297965/fonc-15-1532564-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f738/11891050/a724b966029e/fonc-15-1532564-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f738/11891050/877bba22c256/fonc-15-1532564-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f738/11891050/3d0f81724521/fonc-15-1532564-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f738/11891050/57ff6b72f7b2/fonc-15-1532564-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f738/11891050/54769ac384bb/fonc-15-1532564-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f738/11891050/e56c459fc34e/fonc-15-1532564-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f738/11891050/b9a5d5363a84/fonc-15-1532564-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f738/11891050/5d7099297965/fonc-15-1532564-g008.jpg

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