SNRNP70 regulates the splicing of CD55 to promote osteosarcoma progression.

IF 6.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Wenyue Li, Linzhu Wang, Wen Tian, Weihang Ji, Danyang Bing, Yan Wang, Bingqian Xu, Jiayue Feng, Peng Zhang, Haihai Liang, Yunyan Gu, Baofeng Yang
{"title":"SNRNP70 regulates the splicing of CD55 to promote osteosarcoma progression.","authors":"Wenyue Li, Linzhu Wang, Wen Tian, Weihang Ji, Danyang Bing, Yan Wang, Bingqian Xu, Jiayue Feng, Peng Zhang, Haihai Liang, Yunyan Gu, Baofeng Yang","doi":"10.1172/jci.insight.185269","DOIUrl":null,"url":null,"abstract":"<p><p>Osteosarcoma (OS) is the most common malignant bone tumor, characterized by a high propensity for metastasis. Recent studies have highlighted the role of alternative splicing in cancer metastasis, although the precise mechanisms underlying aberrant splicing in OS invasion and metastasis remain unclear. Here, we analyzed consistently differentially expressed genes and differentially alternative splicing events between primary and metastatic OS to identify potential genes associated with OS progression. U1 small nuclear ribonucleoprotein 70K (SNRNP70) emerged as both differentially expressed and spliced, with elevated SNRNP70 levels correlating with poor prognosis in pateints with OS. Functional experiments demonstrated that SNRNP70 overexpression enhanced the proliferation and metastasis of OS cells in vitro, while its depletion reduced these capabilities in vivo. Mechanistically, SNRNP70 directly interacted with CD55, modulating its alternative splicing and promoting tumor progression in OS. Additionally, metastatic OS samples exhibited increased infiltration of resting immune cells, and single-cell RNA sequencing revealed communication between SNRNP70-expressing osteoblastic cells and macrophages via the ADGRE5/CD55 signaling pathway. Overall, our results showed that SNRNP70 knockdown inhibited OS progression, which was associated with the splicing of CD55, indicating SNRNP70 as a promising target for OS treatment.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":"9 24","pages":""},"PeriodicalIF":6.3000,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JCI insight","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1172/jci.insight.185269","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0

Abstract

Osteosarcoma (OS) is the most common malignant bone tumor, characterized by a high propensity for metastasis. Recent studies have highlighted the role of alternative splicing in cancer metastasis, although the precise mechanisms underlying aberrant splicing in OS invasion and metastasis remain unclear. Here, we analyzed consistently differentially expressed genes and differentially alternative splicing events between primary and metastatic OS to identify potential genes associated with OS progression. U1 small nuclear ribonucleoprotein 70K (SNRNP70) emerged as both differentially expressed and spliced, with elevated SNRNP70 levels correlating with poor prognosis in pateints with OS. Functional experiments demonstrated that SNRNP70 overexpression enhanced the proliferation and metastasis of OS cells in vitro, while its depletion reduced these capabilities in vivo. Mechanistically, SNRNP70 directly interacted with CD55, modulating its alternative splicing and promoting tumor progression in OS. Additionally, metastatic OS samples exhibited increased infiltration of resting immune cells, and single-cell RNA sequencing revealed communication between SNRNP70-expressing osteoblastic cells and macrophages via the ADGRE5/CD55 signaling pathway. Overall, our results showed that SNRNP70 knockdown inhibited OS progression, which was associated with the splicing of CD55, indicating SNRNP70 as a promising target for OS treatment.

求助全文
约1分钟内获得全文 求助全文
来源期刊
JCI insight
JCI insight Medicine-General Medicine
CiteScore
13.70
自引率
1.20%
发文量
543
审稿时长
6 weeks
期刊介绍: JCI Insight is a Gold Open Access journal with a 2022 Impact Factor of 8.0. It publishes high-quality studies in various biomedical specialties, such as autoimmunity, gastroenterology, immunology, metabolism, nephrology, neuroscience, oncology, pulmonology, and vascular biology. The journal focuses on clinically relevant basic and translational research that contributes to the understanding of disease biology and treatment. JCI Insight is self-published by the American Society for Clinical Investigation (ASCI), a nonprofit honor organization of physician-scientists founded in 1908, and it helps fulfill the ASCI's mission to advance medical science through the publication of clinically relevant research reports.
×
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:481959085
Book学术官方微信