N6-methyladenosine regulator YTHDF1 represses the CD8 + T cell-mediated antitumor immunity and ferroptosis in prostate cancer via m6A/PD-L1 manner

IF 6.1 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Apoptosis Pub Date : 2023-09-12 DOI:10.1007/s10495-023-01885-7
Yibing Wang, Peng Jin, Xia Wang
{"title":"N6-methyladenosine regulator YTHDF1 represses the CD8 + T cell-mediated antitumor immunity and ferroptosis in prostate cancer via m6A/PD-L1 manner","authors":"Yibing Wang,&nbsp;Peng Jin,&nbsp;Xia Wang","doi":"10.1007/s10495-023-01885-7","DOIUrl":null,"url":null,"abstract":"<div><p>Increasing data and literature have illustrated that tumor immune escape represents a major source of tumor formation and recrudesce. Besides, novel findings also indicate that RNA N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) participates in the human cancer immune escape. Here, our study investigated the functions of m<sup>6</sup>A reader YTHDF1 in prostate cancer (PCa) immune response and explored the functional mechanism. Results reported that YTHDF1 up-regulated in PCa samples and was closely correlated to poor clinical prognosis. Functionally, YTHDF1 inhibited the killing activity of CD8 + T cells to PCa cells, and moreover mitigated the ferroptosis. Mechanistically, PD-L1 acted as the target of YTHDF1, and YTHDF1 upregulated the transcriptional activity of PD-L1 mRNA. Collectively, YTHDF1 promoted functional PD-L1 partially through enhancing its transcriptional stability, which was necessary for PCa cells to evade effector T cell cytotoxicity and CD8 + T cells mediated ferroptosis. In conclusion, these findings indicate that YTHDF1 represses the CD8 + T cell-mediated antitumor immunity and ferroptosis in PCa via m<sup>6</sup>A-PD-L1 manner, which may provide novel insight for PCa immunotherapy.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 1-2","pages":"142 - 153"},"PeriodicalIF":6.1000,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Apoptosis","FirstCategoryId":"99","ListUrlMain":"https://link.springer.com/article/10.1007/s10495-023-01885-7","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Increasing data and literature have illustrated that tumor immune escape represents a major source of tumor formation and recrudesce. Besides, novel findings also indicate that RNA N6-methyladenosine (m6A) participates in the human cancer immune escape. Here, our study investigated the functions of m6A reader YTHDF1 in prostate cancer (PCa) immune response and explored the functional mechanism. Results reported that YTHDF1 up-regulated in PCa samples and was closely correlated to poor clinical prognosis. Functionally, YTHDF1 inhibited the killing activity of CD8 + T cells to PCa cells, and moreover mitigated the ferroptosis. Mechanistically, PD-L1 acted as the target of YTHDF1, and YTHDF1 upregulated the transcriptional activity of PD-L1 mRNA. Collectively, YTHDF1 promoted functional PD-L1 partially through enhancing its transcriptional stability, which was necessary for PCa cells to evade effector T cell cytotoxicity and CD8 + T cells mediated ferroptosis. In conclusion, these findings indicate that YTHDF1 represses the CD8 + T cell-mediated antitumor immunity and ferroptosis in PCa via m6A-PD-L1 manner, which may provide novel insight for PCa immunotherapy.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
N6-甲基腺苷调节因子YTHDF1通过m6A/PD-L1方式抑制CD8 + T细胞介导的前列腺癌抗肿瘤免疫和铁蛋白沉积。
越来越多的数据和文献表明,肿瘤免疫逃逸是肿瘤形成和复发的主要根源。此外,新的研究结果还表明,RNA N6-甲基腺苷(m6A)参与了人类癌症的免疫逃逸。在此,我们研究了m6A阅读器YTHDF1在前列腺癌(PCa)免疫应答中的功能,并探讨了其功能机制。结果发现,YTHDF1在PCa样本中上调,并与不良临床预后密切相关。在功能上,YTHDF1抑制了CD8 + T细胞对PCa细胞的杀伤活性,并减轻了铁突变。从机制上看,PD-L1是YTHDF1的靶点,YTHDF1上调了PD-L1 mRNA的转录活性。总之,YTHDF1通过增强PD-L1的转录稳定性部分促进了PD-L1的功能,这是PCa细胞逃避效应T细胞细胞毒性和CD8 + T细胞介导的铁突变所必需的。总之,这些研究结果表明,YTHDF1通过m6A-PD-L1的方式抑制了CD8 + T细胞介导的PCa抗肿瘤免疫和铁细胞凋亡,这可能会为PCa免疫疗法提供新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Apoptosis
Apoptosis 生物-生化与分子生物学
CiteScore
9.10
自引率
4.20%
发文量
85
审稿时长
1 months
期刊介绍: Apoptosis, a monthly international peer-reviewed journal, focuses on the rapid publication of innovative investigations into programmed cell death. The journal aims to stimulate research on the mechanisms and role of apoptosis in various human diseases, such as cancer, autoimmune disease, viral infection, AIDS, cardiovascular disease, neurodegenerative disorders, osteoporosis, and aging. The Editor-In-Chief acknowledges the importance of advancing clinical therapies for apoptosis-related diseases. Apoptosis considers Original Articles, Reviews, Short Communications, Letters to the Editor, and Book Reviews for publication.
期刊最新文献
Isolation, identification, and challenges of extracellular vesicles: emerging players in clinical applications. Lenvatinib inhibits cholangiocarcinoma progression by targeting the FGF19/PI3K/AKT signaling pathway. Advancements in programmed cell death research in antitumor therapy: a comprehensive overview. Dysregulation of R-loop homeostasis shapes the immunosuppressive microenvironment and induces malignant progression in melanoma. FBXO2 as a switch guides a special fate of tumor clones evolving into a highly malignant transcriptional subtype in oral squamous cell carcinoma.
×
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
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 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 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1