MiR-17∼92 is involved in NF-κB activation via targeting the ubiquitin-editing proteins to mediate RIP1 complex polyubiquitinations in ABC-DLBCL

IF 4.5 3区 医学 Q2 IMMUNOLOGY Clinical immunology Pub Date : 2024-06-22 DOI:10.1016/j.clim.2024.110297
Xiaoyan Zhang , Xuan Zhang , Xin Huang , Javeed Iqbal , Timothy W. McKeithan , Wing C. Chan , Julie M. Vose , Chengfeng Bi , Xiaofan Zhu , Kai Fu
{"title":"MiR-17∼92 is involved in NF-κB activation via targeting the ubiquitin-editing proteins to mediate RIP1 complex polyubiquitinations in ABC-DLBCL","authors":"Xiaoyan Zhang ,&nbsp;Xuan Zhang ,&nbsp;Xin Huang ,&nbsp;Javeed Iqbal ,&nbsp;Timothy W. McKeithan ,&nbsp;Wing C. Chan ,&nbsp;Julie M. Vose ,&nbsp;Chengfeng Bi ,&nbsp;Xiaofan Zhu ,&nbsp;Kai Fu","doi":"10.1016/j.clim.2024.110297","DOIUrl":null,"url":null,"abstract":"<div><p>Activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is an aggressive lymphoma characterized by constitutive NF-κB activation, but whether miR-17∼92 contributes to this activation remains unclear. Herein, we sought to evaluate the role of miR-17∼92 in the process of NF-κB activation in ABC-DLBCL. We found that the expression of miR-17∼92 primary transcript was positively correlated with NF-κB activity, miR-17∼92 activated the NF-κB signaling in ABC-DLBCL, and its over-expression promoted ABC-DLBCL cell growth, accelerated cell G1 to S phase transition and enhanced cell resistance to NF-κB inhibitor. Importantly, miR-17∼92 promoted NF-κB activation through directly targeting multiple ubiquitin-editing regulators to lead to increase the K63-linked polyubiquitination and decrease the K48-linked polyubiquitination of RIP1 complex in ABC-DLBCL. We further found that miR-17∼92 selectively activated IκB-α and NF-κB p65 but not NF-κB p52/p100, and high miR-17∼92 expression was also associated with poorer outcome in ABC-DLBCL patients. Overall, our results showed that miR-17∼92 selectively activated the canonical NF-κB signaling via targeting ubiquitin-editing regulators to lead to constitutively NF-κB activation and poorer outcome in ABC-DLBCL. These findings uncovered an innovative function of miR-17∼92 and previously unappreciated regulatory mechanism of NF-κB activation in ABC-DLBCL. Targeting miR-17∼92 may thus provide a novel bio-therapeutic strategy for ABC-DLBCL patients.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"265 ","pages":"Article 110297"},"PeriodicalIF":4.5000,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1521661624004066","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is an aggressive lymphoma characterized by constitutive NF-κB activation, but whether miR-17∼92 contributes to this activation remains unclear. Herein, we sought to evaluate the role of miR-17∼92 in the process of NF-κB activation in ABC-DLBCL. We found that the expression of miR-17∼92 primary transcript was positively correlated with NF-κB activity, miR-17∼92 activated the NF-κB signaling in ABC-DLBCL, and its over-expression promoted ABC-DLBCL cell growth, accelerated cell G1 to S phase transition and enhanced cell resistance to NF-κB inhibitor. Importantly, miR-17∼92 promoted NF-κB activation through directly targeting multiple ubiquitin-editing regulators to lead to increase the K63-linked polyubiquitination and decrease the K48-linked polyubiquitination of RIP1 complex in ABC-DLBCL. We further found that miR-17∼92 selectively activated IκB-α and NF-κB p65 but not NF-κB p52/p100, and high miR-17∼92 expression was also associated with poorer outcome in ABC-DLBCL patients. Overall, our results showed that miR-17∼92 selectively activated the canonical NF-κB signaling via targeting ubiquitin-editing regulators to lead to constitutively NF-κB activation and poorer outcome in ABC-DLBCL. These findings uncovered an innovative function of miR-17∼92 and previously unappreciated regulatory mechanism of NF-κB activation in ABC-DLBCL. Targeting miR-17∼92 may thus provide a novel bio-therapeutic strategy for ABC-DLBCL patients.

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 ABC-DLBCL 中,MiR-17~92 通过靶向泛素编辑蛋白介导 RIP1 复合物多泛素化参与 NF-κB 激活。
活化B细胞样弥漫大B细胞淋巴瘤(ABC-DLBCL)是一种侵袭性淋巴瘤,其特点是构成性NF-κB活化,但miR-17~92是否有助于这种活化仍不清楚。在此,我们试图评估 miR-17~92 在 ABC-DLBCL 中 NF-κB 激活过程中的作用。我们发现,miR-17~92主转录本的表达与NF-κB活性呈正相关,miR-17~92激活了ABC-DLBCL中的NF-κB信号转导,它的过度表达促进了ABC-DLBCL细胞的生长,加速了细胞G1期向S期的转变,增强了细胞对NF-κB抑制剂的抵抗力。重要的是,miR-17~92 通过直接靶向多个泛素编辑调节因子,导致 ABC-DLBCL 中 RIP1 复合物的 K63 连接泛素化增加和 K48 连接泛素化减少,从而促进了 NF-κB 的激活。我们进一步发现,miR-17~92能选择性地激活IκB-α和NF-κB p65,但不能激活NF-κB p52/p100,而且miR-17~92的高表达与ABC-DLBCL患者较差的预后有关。总之,我们的研究结果表明,miR-17~92通过靶向泛素编辑调节因子选择性地激活了典型的NF-κB信号传导,从而导致了ABC-DLBCL患者NF-κB的组成性激活和较差的预后。这些发现揭示了miR-17~92的创新功能,以及之前未被认识到的ABC-DLBCL中NF-κB激活的调控机制。因此,靶向miR-17~92可为ABC-DLBCL患者提供一种新的生物治疗策略。
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
Clinical immunology
Clinical immunology 医学-免疫学
CiteScore
12.30
自引率
1.20%
发文量
212
审稿时长
34 days
期刊介绍: Clinical Immunology publishes original research delving into the molecular and cellular foundations of immunological diseases. Additionally, the journal includes reviews covering timely subjects in basic immunology, along with case reports and letters to the editor.
期刊最新文献
A randomised, placebo-controlled, phase III trial of leniolisib in activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS): Adolescent and adult subgroup analysis. Clinical characterization of NOD2 variants in patients with common variable immunodeficiency. HLA evolutionary divergence effect on bacterial infection risk in cirrhotic liver transplant candidates. Optimizing iNKT-driven immune responses against cancer by modulating CD1d in tumor and antigen presenting cells. Comparative analysis of the B cell receptor repertoire during relapse and remission in patients with multiple sclerosis.
×
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