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

IF 5.3 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

{"title":"Cancer-secreted exosomal miR-1825 induces angiogenesis to promote colorectal cancer metastasis.","authors":"Jingbo Sun, Junjie Luo, Jialong Liu, Hongmei Wu, Yanyan Li, Yangwei Xu, Lixin Liu, Xiaolong Liu, Qingling Zhang","doi":"10.1186/s12935-025-03674-5","DOIUrl":null,"url":null,"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.","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"63"},"PeriodicalIF":5.3000,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847347/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cell International","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12935-025-03674-5","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

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.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

求助全文

约1分钟内获得全文去求助

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.