Cancer-secreted exosomal miR-1825 induces angiogenesis to promote colorectal cancer metastasis.

IF 6 2区医学 Q1 ONCOLOGY Cancer Cell International Pub Date : 2025-02-22 DOI:10.1186/s12935-025-03674-5

Jingbo Sun, Junjie Luo, Jialong Liu, Hongmei Wu, Yanyan Li, Yangwei Xu, Lixin Liu, Xiaolong Liu, Qingling Zhang

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Abstract

Background: Angiogenesis is one of the important factors related to tumorigenesis, invasion, and metastasis. Cancer-secreted exosomes are essential mediators of intercellular cross-talk and participate in angiogenesis and metastasis. Unveiling the mechanism of angiogenesis is an important way to develop anti-angiogenesis therapeutic strategies to against cancer progression.

Methods: miR-1825 expression and relationship with microvascular density were validated in colorectal cancer (CRC) by in situ hybridization (ISH) staining and immunohistochemistry (IHC). Sequential differential centrifugation, transmission electron microscopy, and western blotting analysis were used to extract and characterize exosomes. The effort of exosomal miR-1825 on endothelial cells was examined by transwell assay, wound healing assay, tube formation assay, and aortic ring assay. The relationship of miR-1825, ING1 and the downstream pathway were analyzed by western blot, RT-PCR, Immunofluorescence, and dual-luciferase reporter system analysis.

Results: Exosomal miR-1825 is associated with angiogenesis in CRC and is enriched in exosomes extracted from the serum of CRC patients. The CRC-secreted exosomal miR-1825 can be transferred into vascular endothelial cells, promoting endothelial cell migration and tube formation in vitro, and facilitating angiogenesis and tumor metastasis in vivo. Mechanistically, exosomal miR-1825 regulates angiogenesis and tumor metastasis by suppressing inhibitor of growth family member 1 (ING1) and activating the TGF-β/Smad2/Smad3 signaling pathway in the recipient HUVECs.

Conclusions: Our study demonstrated the CRC-secreted exosomal miR-1825 could be transferred to vascular endothelial cells, subsequently leads to the inhibition of ING1 and the activation of the TGF-β/Smad2/Smad3 signaling pathway, thereby promoting angiogenesis and liver metastasis in CRC. Exosomal miR-1825 is thus a potential diagnostic and therapeutic target for CRC patients.

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肿瘤分泌的外泌体miR-1825诱导血管生成促进结直肠癌转移。

背景：血管生成是肿瘤发生、侵袭和转移的重要因素之一。肿瘤分泌的外泌体是细胞间相互作用的重要介质，参与血管生成和转移。揭示血管生成的机制是制定抗血管生成治疗策略以对抗癌症进展的重要途径。方法：通过原位杂交（ISH）染色和免疫组化（IHC）验证miR-1825在结直肠癌（CRC）中的表达及其与微血管密度的关系。序列差速离心，透射电镜和western blotting分析用于提取和表征外泌体。外泌体miR-1825对内皮细胞的作用通过transwell实验、伤口愈合实验、管形成实验和主动脉环实验检测。通过western blot、RT-PCR、免疫荧光和双荧光素酶报告系统分析miR-1825、ING1与下游通路的关系。结果：外泌体miR-1825与结直肠癌的血管生成有关，并且在结直肠癌患者血清中提取的外泌体中富集。crc分泌的外泌体miR-1825可以转移到血管内皮细胞中，在体外促进内皮细胞迁移和成管，在体内促进血管生成和肿瘤转移。在机制上，外泌体miR-1825通过抑制受体HUVECs中生长家族成员1抑制剂（ING1）和激活TGF-β/Smad2/Smad3信号通路来调节血管生成和肿瘤转移。结论：我们的研究表明，CRC分泌的外泌体miR-1825可以转移到血管内皮细胞，从而抑制ING1，激活TGF-β/Smad2/Smad3信号通路，从而促进CRC的血管生成和肝脏转移。因此，外泌体miR-1825是CRC患者潜在的诊断和治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.