在骨肉瘤中,CAFs外泌体miR-21-5p抑制铁下垂并促进增殖和迁移。

IF 6 2区 医学 Q1 ONCOLOGY
Xiaoying Niu, Wen Tian, Yuanmeng Ke, Yifan Li, Xinxin Zhang
{"title":"在骨肉瘤中,CAFs外泌体miR-21-5p抑制铁下垂并促进增殖和迁移。","authors":"Xiaoying Niu, Wen Tian, Yuanmeng Ke, Yifan Li, Xinxin Zhang","doi":"10.1186/s12935-025-03930-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Osteosarcoma is one of the malignant tumors in children and adolescents patients. Uncontrolled and unlimited proliferation and metastasis lead to poor overall survival. CAFs play a pivotal role in the osteosarcoma tumor microenvironment, exerting significant influence on prognosis and treatment outcomes. However, there remains a need for further exploration into the intricate molecular mechanisms underlying CAFs.</p><p><strong>Methods: </strong>Single-cell RNA sequencing was employed to characterize the microenvironment of osteosarcoma. Tissue exosomal miRNA sequencing was conducted on tumor tissues and adjacent normal tissues to screen for abnormal expression of exosomal miRNAs. WGCNA analysis was used to identify target exosomal miRNAs. The relative expression of miR-21-5p was analyzed using qRT-PCR. The proliferation rate and migration ability of tumor cells were assessed using the CCK8 and Transwell method, respectively. Exosomes derived from cells were extracted and characterized via transmission electron microscopy and NTA analysis. siRNA interference was utilized to disrupt the expression of miR-21-5p in CAFs. Experiments in vivo validated the role of exosomal miR-21-5p in promoting malignant characteristics in osteosarcoma.</p><p><strong>Results: </strong>Single-cell RNA sequencing analysis of GSE162454 revealed the crucial role of CAFs in the pathogenesis of osteosarcoma. Tissue exosomal miRNA sequencing unveiled significant differential expression of miR-21-5p. Subsequently, aberrant upregulation of exosomal miR-21-5p exhibited a strong correlation with advanced clinical stage and poor prognosis in osteosarcoma. Further experiments in vitro indicated that elevated levels of miR-21-5p significantly enhanced proliferation and migration of osteosarcoma cells by suppressing ferroptosis. Moreover, experiments in vivo validated the capacity of CAFs-derived exosomal miR-21-5p to promote tumor growth and weight, thereby demonstrating their ability to deliver miR-21-5p to osteosarcoma cells and induce proliferation and migration through inhibition of ferroptosis.</p><p><strong>Conclusions: </strong>Our findings indicate that exosomal miR-21-5p could potentially serve as a therapeutic target in osteosarcoma, providing initial evidence for further clinical investigation.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"308"},"PeriodicalIF":6.0000,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12362868/pdf/","citationCount":"0","resultStr":"{\"title\":\"CAFs exosomal miR-21-5p suppresses ferroptosis and promotes proliferation and migration in osteosarcoma.\",\"authors\":\"Xiaoying Niu, Wen Tian, Yuanmeng Ke, Yifan Li, Xinxin Zhang\",\"doi\":\"10.1186/s12935-025-03930-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Osteosarcoma is one of the malignant tumors in children and adolescents patients. Uncontrolled and unlimited proliferation and metastasis lead to poor overall survival. CAFs play a pivotal role in the osteosarcoma tumor microenvironment, exerting significant influence on prognosis and treatment outcomes. However, there remains a need for further exploration into the intricate molecular mechanisms underlying CAFs.</p><p><strong>Methods: </strong>Single-cell RNA sequencing was employed to characterize the microenvironment of osteosarcoma. Tissue exosomal miRNA sequencing was conducted on tumor tissues and adjacent normal tissues to screen for abnormal expression of exosomal miRNAs. WGCNA analysis was used to identify target exosomal miRNAs. The relative expression of miR-21-5p was analyzed using qRT-PCR. The proliferation rate and migration ability of tumor cells were assessed using the CCK8 and Transwell method, respectively. Exosomes derived from cells were extracted and characterized via transmission electron microscopy and NTA analysis. siRNA interference was utilized to disrupt the expression of miR-21-5p in CAFs. Experiments in vivo validated the role of exosomal miR-21-5p in promoting malignant characteristics in osteosarcoma.</p><p><strong>Results: </strong>Single-cell RNA sequencing analysis of GSE162454 revealed the crucial role of CAFs in the pathogenesis of osteosarcoma. Tissue exosomal miRNA sequencing unveiled significant differential expression of miR-21-5p. Subsequently, aberrant upregulation of exosomal miR-21-5p exhibited a strong correlation with advanced clinical stage and poor prognosis in osteosarcoma. Further experiments in vitro indicated that elevated levels of miR-21-5p significantly enhanced proliferation and migration of osteosarcoma cells by suppressing ferroptosis. Moreover, experiments in vivo validated the capacity of CAFs-derived exosomal miR-21-5p to promote tumor growth and weight, thereby demonstrating their ability to deliver miR-21-5p to osteosarcoma cells and induce proliferation and migration through inhibition of ferroptosis.</p><p><strong>Conclusions: </strong>Our findings indicate that exosomal miR-21-5p could potentially serve as a therapeutic target in osteosarcoma, providing initial evidence for further clinical investigation.</p>\",\"PeriodicalId\":9385,\"journal\":{\"name\":\"Cancer Cell International\",\"volume\":\"25 1\",\"pages\":\"308\"},\"PeriodicalIF\":6.0000,\"publicationDate\":\"2025-08-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12362868/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Cell International\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12935-025-03930-8\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cell International","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12935-025-03930-8","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

摘要

背景:骨肉瘤是儿童和青少年多发的恶性肿瘤之一。不受控制和无限制的增殖和转移导致较差的总生存率。CAFs在骨肉瘤肿瘤微环境中起着举足轻重的作用,对骨肉瘤的预后和治疗效果有重要影响。然而,仍有必要进一步探索复杂的分子机制。方法:采用单细胞RNA测序技术对骨肉瘤的微环境进行表征。对肿瘤组织及邻近正常组织进行组织外泌体miRNA测序,筛查外泌体miRNA的异常表达。WGCNA分析用于鉴定靶外泌体mirna。采用qRT-PCR分析miR-21-5p的相对表达。采用CCK8法和Transwell法分别测定肿瘤细胞的增殖率和迁移能力。从细胞中提取外泌体,并通过透射电镜和NTA分析进行表征。利用siRNA干扰破坏miR-21-5p在CAFs中的表达。体内实验验证了外泌体miR-21-5p在促进骨肉瘤恶性特征中的作用。结果:GSE162454的单细胞RNA测序分析揭示了CAFs在骨肉瘤发病机制中的关键作用。组织外泌体miRNA测序揭示了miR-21-5p的显著差异表达。随后,外泌体miR-21-5p的异常上调与骨肉瘤的晚期临床分期和不良预后有很强的相关性。进一步的体外实验表明,miR-21-5p水平升高通过抑制铁下垂显著增强骨肉瘤细胞的增殖和迁移。此外,体内实验验证了cafs来源的外泌体miR-21-5p促进肿瘤生长和体重的能力,从而证明了它们能够将miR-21-5p传递给骨肉瘤细胞,并通过抑制铁下垂诱导增殖和迁移。结论:我们的研究结果表明,外泌体miR-21-5p可能作为骨肉瘤的治疗靶点,为进一步的临床研究提供了初步证据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
CAFs exosomal miR-21-5p suppresses ferroptosis and promotes proliferation and migration in osteosarcoma.

Background: Osteosarcoma is one of the malignant tumors in children and adolescents patients. Uncontrolled and unlimited proliferation and metastasis lead to poor overall survival. CAFs play a pivotal role in the osteosarcoma tumor microenvironment, exerting significant influence on prognosis and treatment outcomes. However, there remains a need for further exploration into the intricate molecular mechanisms underlying CAFs.

Methods: Single-cell RNA sequencing was employed to characterize the microenvironment of osteosarcoma. Tissue exosomal miRNA sequencing was conducted on tumor tissues and adjacent normal tissues to screen for abnormal expression of exosomal miRNAs. WGCNA analysis was used to identify target exosomal miRNAs. The relative expression of miR-21-5p was analyzed using qRT-PCR. The proliferation rate and migration ability of tumor cells were assessed using the CCK8 and Transwell method, respectively. Exosomes derived from cells were extracted and characterized via transmission electron microscopy and NTA analysis. siRNA interference was utilized to disrupt the expression of miR-21-5p in CAFs. Experiments in vivo validated the role of exosomal miR-21-5p in promoting malignant characteristics in osteosarcoma.

Results: Single-cell RNA sequencing analysis of GSE162454 revealed the crucial role of CAFs in the pathogenesis of osteosarcoma. Tissue exosomal miRNA sequencing unveiled significant differential expression of miR-21-5p. Subsequently, aberrant upregulation of exosomal miR-21-5p exhibited a strong correlation with advanced clinical stage and poor prognosis in osteosarcoma. Further experiments in vitro indicated that elevated levels of miR-21-5p significantly enhanced proliferation and migration of osteosarcoma cells by suppressing ferroptosis. Moreover, experiments in vivo validated the capacity of CAFs-derived exosomal miR-21-5p to promote tumor growth and weight, thereby demonstrating their ability to deliver miR-21-5p to osteosarcoma cells and induce proliferation and migration through inhibition of ferroptosis.

Conclusions: Our findings indicate that exosomal miR-21-5p could potentially serve as a therapeutic target in osteosarcoma, providing initial evidence for further clinical investigation.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
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.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信