RNA Shielding of p65 Is Required to Potentiate Oncogenic Inflammation in TET2-Mutated Clonal Hematopoiesis.

IF 33.3 1区 医学 Q1 ONCOLOGY Cancer discovery Pub Date : 2024-12-02 DOI:10.1158/2159-8290.CD-24-0093
Nana Adjoa Ben-Crentsil, Wazim Mohammed Ismail, Maria E Balasis, Hannah Newman, Ariel Quintana, Moritz Binder, Traci Kruer, Surendra Neupane, Meghan C Ferrall-Fairbanks, Jenna Fernandez, Terra L Lasho, Christy M Finke, Mohammed L Ibrahim, Kathy L McGraw, Michael Wysota, Amy L Aldrich, Christopher B Ryder, Christopher T Letson, Joshua Traina, Amy F McLemore, Nathalie Droin, Aditi Shastri, Seongseok Yun, Eric Solary, David A Sallman, Amer A Beg, Li Ma, Alexandre Gaspar-Maia, Mrinal M Patnaik, Eric Padron
{"title":"RNA Shielding of p65 Is Required to Potentiate Oncogenic Inflammation in TET2-Mutated Clonal Hematopoiesis.","authors":"Nana Adjoa Ben-Crentsil, Wazim Mohammed Ismail, Maria E Balasis, Hannah Newman, Ariel Quintana, Moritz Binder, Traci Kruer, Surendra Neupane, Meghan C Ferrall-Fairbanks, Jenna Fernandez, Terra L Lasho, Christy M Finke, Mohammed L Ibrahim, Kathy L McGraw, Michael Wysota, Amy L Aldrich, Christopher B Ryder, Christopher T Letson, Joshua Traina, Amy F McLemore, Nathalie Droin, Aditi Shastri, Seongseok Yun, Eric Solary, David A Sallman, Amer A Beg, Li Ma, Alexandre Gaspar-Maia, Mrinal M Patnaik, Eric Padron","doi":"10.1158/2159-8290.CD-24-0093","DOIUrl":null,"url":null,"abstract":"<p><strong>Significance: </strong>This work identifies MALAT1 as a requisite downstream effector of oncogenic feedforward inflammatory circuits necessary for the development of TET2-mutated CH and fulminant myeloid malignancy. We elucidate a novel mechanism by which MALAT1 \"shields\" p65 from dephosphorylation to potentiate this circuit and nominate MALAT1 inhibition as a future therapeutic strategy.</p>","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":"2509-2531"},"PeriodicalIF":33.3000,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11611684/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer discovery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1158/2159-8290.CD-24-0093","RegionNum":1,"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

Significance: This work identifies MALAT1 as a requisite downstream effector of oncogenic feedforward inflammatory circuits necessary for the development of TET2-mutated CH and fulminant myeloid malignancy. We elucidate a novel mechanism by which MALAT1 "shields" p65 from dephosphorylation to potentiate this circuit and nominate MALAT1 inhibition as a future therapeutic strategy.

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
在 TET2 突变的克隆造血过程中,需要 P65 的 RNA 屏蔽来增强致癌炎症。
TET2突变(mTET2)是髓系恶性肿瘤和克隆性造血(CH)中常见的遗传事件。这些突变发生在创始克隆中,与许多与致癌前馈炎症回路相关的临床后遗症有牵连。然而,mTET2 的直接下游效应器对这种炎症回路的增效作用尚不清楚。为了解决这个问题,我们在有或没有 TET2 基因突变的 COVID-19 患者中进行了 scRNA 和 scATAC-seq,理由是 COVID-19 引起的炎症可能会突出 mTET2 的关键下游转录靶标。利用这种方法,我们确定了可用于治疗的 lncRNA MALAT1,它是 mTET2 的核心下游效应物,对于诱导 mTET2 在体内的致癌促炎特征是必要且充分的。我们还阐明了 mTET2 上调 MALAT1 的机制,并描述了 MALAT1 与 P65 之间的相互作用,这种相互作用会导致 RNA "屏蔽 "PP2A 的去磷酸化,从而阻止炎症信号的传递。
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
Cancer discovery
Cancer discovery ONCOLOGY-
CiteScore
22.90
自引率
1.40%
发文量
838
审稿时长
6-12 weeks
期刊介绍: Cancer Discovery publishes high-impact, peer-reviewed articles detailing significant advances in both research and clinical trials. Serving as a premier cancer information resource, the journal also features Review Articles, Perspectives, Commentaries, News stories, and Research Watch summaries to keep readers abreast of the latest findings in the field. Covering a wide range of topics, from laboratory research to clinical trials and epidemiologic studies, Cancer Discovery spans the entire spectrum of cancer research and medicine.
期刊最新文献
The oncogenic EGFR-SHC1 fusion confers insensitivity to EGFR-TKI via dual activation of N-EGFR kinase domain and C-SHC1 phosphorylation sites in lung cancer. Same-Slide Spatial Multi-Omics Integration with IN-DEPTH Reveals Tumor Virus-Linked Spatial Reorganization of the Tumor Microenvironment. Winning Cancer Grand Challenges Teams Announced. Nearly 40% of Cancers Could Be Prevented. More Questions Than Answers in Trial of GRAIL's Galleri.
×
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:604180095
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