Loss of RBM45 inhibits breast cancer progression by reducing the SUMOylation of IRF7 to promote IFNB1 transcription.
Cancer Lett
; 596: 216988, 2024 Aug 01.
Article
en En
| MEDLINE
| ID: mdl-38797234
ABSTRACT
Type I interferons exhibit anti-proliferative and anti-cancer activities, but their detailed regulatory mechanisms in cancer have not been fully elucidated yet. RNA binding proteins are master orchestrators of gene regulation, which are closely related to tumor progression. Here we show that the upregulated RNA binding protein RBM45 correlates with poor prognosis in breast cancer. Depletion of RBM45 suppresses breast cancer progression both in cultured cells and xenograft mouse models. Mechanistically, RBM45 ablation inhibits breast cancer progression through regulating type I interferon signaling, particularly by elevating IFN-ß production. Importantly, RBM45 recruits TRIM28 to IRF7 and stimulates its SUMOylation, thereby repressing IFNB1 transcription. Loss of RBM45 reduced the SUMOylation of IRF7 by reducing the interaction between TRIM28 and IRF7 to promote IFNB1 transcription, leading to the inhibition of breast cancer progression. Taken together, our finding uncovers a vital role of RBM45 in modulating type I interferon signaling and cancer aggressive progression, implicating RBM45 as a potential therapeutic target in breast cancer.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Regulación Neoplásica de la Expresión Génica
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Proteínas de Unión al ARN
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Progresión de la Enfermedad
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Factor 7 Regulador del Interferón
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Sumoilación
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cancer Lett
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Irlanda