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

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

Copyright © 2024 Elsevier Inc. All rights reserved.

Détails bibliographiques
Publié dans:Clinical immunology (Orlando, Fla.). - 1999. - 265(2024) vom: 15. Aug., Seite 110297
Auteur principal: Zhang, Xiaoyan (Auteur)
Autres auteurs: Zhang, Xuan, Huang, Xin, Iqbal, Javeed, McKeithan, Timothy W, Chan, Wing C, Vose, Julie M, Bi, Chengfeng, Zhu, Xiaofan, Fu, Kai
Format: Article en ligne
Langue:English
Publié: 2024
Accès à la collection:Clinical immunology (Orlando, Fla.)
Sujets:Journal Article ABC-DLBCL NF-κB Polyubiquitination Ubiquitin-editing proteins miR-17∼92 MicroRNAs NF-kappa B AGFG1 protein, human RNA-Binding Proteins plus... MIR17HG, human Nuclear Pore Complex Proteins RNA, Long Noncoding
Description
Résumé:Copyright © 2024 Elsevier Inc. All rights reserved.
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
Description:Date Completed 19.07.2024
Date Revised 22.07.2024
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2024.110297