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miR-29在调节肿瘤血管生成中的潜力:综述

The potential of miR-29 in modulating tumor angiogenesis: a comprehensive review.

作者信息

Zhou Rui-Ting, Luo Xiao-Jie, Zhang Xiao-Xin-Ran, Wu Jiang-Feng, Ni Yi-Ran

机构信息

Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Daxue Road 8#, Yichang, 443002, Hubei, China.

College of Basic Medical Science, China Three Gorges University, Yichang, 443002, China.

出版信息

Discov Oncol. 2025 Apr 6;16(1):474. doi: 10.1007/s12672-025-02246-3.

Abstract

MicroRNAs (miRNAs) are a class of short non-coding RNAs that play a crucial role in the post-transcriptional regulation of gene expression. They are associated with various biological processes related to tumors. Among the numerous miRNAs, miR-29 has garnered attention for its role in regulating tumor angiogenesis. In numerous human tumors, miR-29 has been demonstrated to negatively correlate with the capacity for angiogenesis and the degree of malignancy, as well as with the expression levels of pro-angiogenic factors such as vascular endothelial growth factor vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and matrix metalloproteinase (MMP)-2. Multiple studies, utilizing techniques like dual-luciferase reporter assays, have confirmed that miR-29 directly targets the 3'-untranslated region (UTR) of mRNAs for VEGF, PDGF, and MMP-2. Extensive investigations involving tumor cell lines and animal models have shown that the overexpression of miR-29, achieved through miRNA transfection or the introduction of miRNA mimics, effectively inhibits angiogenesis by upregulating these pro-angiogenic factors. Conversely, downregulation of miR-29 using specific inhibitors promotes angiogenesis. While small molecule inhibitors and antibodies targeting VEGF constitute a primary strategy in anti-angiogenesis therapies, miR-29's ability to target multiple pro-angiogenic molecules positions it as a promising candidate for future therapeutic interventions, especially with ongoing advancements in nucleic acid drug design and delivery systems.

摘要

微小RNA(miRNA)是一类短链非编码RNA,在基因表达的转录后调控中发挥着关键作用。它们与肿瘤相关的各种生物学过程有关。在众多的miRNA中,miR-29因其在调节肿瘤血管生成中的作用而受到关注。在许多人类肿瘤中,miR-29已被证明与血管生成能力、恶性程度以及血管内皮生长因子(VEGF)、血小板衍生生长因子(PDGF)和基质金属蛋白酶(MMP)-2等促血管生成因子的表达水平呈负相关。多项研究利用双荧光素酶报告基因检测等技术证实,miR-29直接靶向VEGF、PDGF和MMP-2的mRNA的3'非翻译区(UTR)。涉及肿瘤细胞系和动物模型的大量研究表明,通过miRNA转染或引入miRNA模拟物实现miR-29的过表达,可通过上调这些促血管生成因子有效抑制血管生成。相反,使用特异性抑制剂下调miR-29可促进血管生成。虽然靶向VEGF的小分子抑制剂和抗体是抗血管生成治疗的主要策略,但miR-29靶向多种促血管生成分子的能力使其成为未来治疗干预的有希望的候选者,特别是随着核酸药物设计和递送系统的不断进步。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e500/11973036/69b4db4bb40f/12672_2025_2246_Fig1_HTML.jpg

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