MiR-17â¼92 is involved in NF-κB activation via targeting the ubiquitin-editing proteins to mediate RIP1 complex polyubiquitinations in ABC-DLBCL.
Clin Immunol
; 265: 110297, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-38909971
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-17â¼92 contributes to this activation remains unclear. Herein, we sought to evaluate the role of miR-17â¼92 in the process of NF-κB activation in ABC-DLBCL. We found that the expression of miR-17â¼92 primary transcript was positively correlated with NF-κB activity, miR-17â¼92 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-17â¼92 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-17â¼92 selectively activated IκB-α and NF-κB p65 but not NF-κB p52/p100, and high miR-17â¼92 expression was also associated with poorer outcome in ABC-DLBCL patients. Overall, our results showed that miR-17â¼92 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-17â¼92 and previously unappreciated regulatory mechanism of NF-κB activation in ABC-DLBCL. Targeting miR-17â¼92 may thus provide a novel bio-therapeutic strategy for ABC-DLBCL patients.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
NF-kappa B
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Linfoma Difuso de Grandes Células B
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MicroRNAs
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Ubiquitinação
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article