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通过外泌体 microRNA 靶向氧化还原信号:对肿瘤微环境与精准肿瘤学的启示

英文原题:Targeting Redox Signaling Through Exosomal MicroRNA: Insights into Tumor Microenvironment and Precision Oncology.

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Targeting Redox Signaling Through Exosomal MicroRNA: Insights into Tumor Microenvironment and Precision Oncology.

PubMed 2025/04/22(内容时间) Antioxidants (Basel) Q1 · IF 8.2(JCR 2025)

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中文摘要

活性氧(ROS)在癌症进展中具有双重作用,既作为信号分子,也可造成氧化损伤。新兴证据揭示,肿瘤微环境(TME)中ROS、微小RNA(miRNA)和外泌体之间存在复杂相互作用,形成调节免疫应答、血管生成和治疗耐药的调控轴。

具体而言,氧化应激不仅刺激外泌体生物发生,还可通过hnRNPA2B1和SYNCRIP等RNA结合蛋白,影响氧化还原敏感性miRNA(miR-21、miR-155和miR-210)的选择性装载。这些miRNA经外泌体递送后,会改变受体细胞基因表达,并促成支持肿瘤的表型,例如M2型巨噬细胞极化、CD8+ T细胞受抑及内皮重塑。本综述系统探讨ROS–miRNA–外泌体轴如何在缺氧和炎症条件下协调免疫细胞与基质细胞群之间的通讯,并重点关注NADPH氧化酶、缺氧诱导因子及自噬相关机制对外泌体输出的调节作用。

此外,我们分析天然产物及姜黄素、白藜芦醇和人参皂苷等草药成分的治疗价值;这些物质在调节ROS水平、miRNA表达和外泌体动态方面显示出良好能力。

我们进一步讨论利用该调控轴治疗癌症的临床潜力,包括间充质干细胞来源外泌体、调节铁死亡和基于miRNA的免疫调节等策略。结合空间转录组学和单细胞分析的见解,本综述为开发以外泌体为中心、调节氧化还原状态的疗法提供机制基础。最终,本文旨在指导未来将草药医学与氧化还原生物学结合用于抗癌的研究和药物发现。

展开英文摘要原文

Reactive oxygen species (ROS) play a dual role in cancer progression, acting as both signaling molecules and drivers of oxidative damage. Emerging evidence highlights the intricate interplay between ROS, microRNAs (miRNAs), and exosomes within the tumor microenvironment (TME), forming a regulatory axis that modulates immune responses, angiogenesis, and therapeutic resistance. In particular, oxidative stress not only stimulates exosome biogenesis but also influences the selective packaging of redox-sensitive miRNAs (miR-21, miR-155, and miR-210) via RNA-binding proteins such as hnRNPA2B1 and SYNCRIP.

These miRNAs, delivered through exosomes, alter gene expression in recipient cells and promote tumor-supportive phenotypes such as M2 macrophage polarization, CD8 + T-cell suppression, and endothelial remodeling. This review systematically explores how this ROS-miRNA-exosome axis orchestrates communication across immune and stromal cell populations under hypoxic and inflammatory conditions. Particular emphasis is placed on the role of NADPH oxidases, hypoxia-inducible factors, and autophagy-related mechanisms in regulating exosomal output.

In addition, we analyze the therapeutic relevance of natural products and herbal compounds-such as curcumin, resveratrol, and ginsenosides-which have demonstrated promising capabilities to modulate ROS levels, miRNA expression, and exosome dynamics.

We further discuss the clinical potential of leveraging this axis for cancer therapy, including strategies involving mesenchymal stem cell-derived exosomes, ferroptosis regulation, and miRNA-based immune modulation.

Incorporating insights from spatial transcriptomics and single-cell analysis, this review provides a mechanistic foundation for the development of exosome-centered, redox-modulating therapeutics. Ultimately, this work aims to guide future research and drug discovery efforts toward integrating herbal medicine and redox biology in the fight against cancer.

论文信息

作者
Park MN、Kim M、Lee S、Kang S、Ahn CH、Tallei TE、Kim W、Kim B
单位
College of Korean Medicine, Kyung Hee University, 1-5 Hoegidong, Dongdaemun-gu, Seoul 02447, Republic of Korea.South Korea
文献类型
综述
期刊
Antioxidants (Basel, Switzerland)2025 Apr 22
原文标识
PubMed 40427384 · DOI 10.3390/antiox14050501