miR-4734 conditionally suppresses ER stress-associated proinflammatory responses.
FEBS Lett
; 597(9): 1233-1245, 2023 05.
Article
em En
| MEDLINE
| ID: mdl-36445168
ABSTRACT
Prolonged metabolic stress can lead to severe pathologies. In metabolically challenged primary fibroblasts, we assigned a novel role for the poorly characterized miR-4734 in restricting ATF4 and IRE1-mediated upregulation of a set of proinflammatory cytokines and endoplasmic reticulum stress-associated genes. Conversely, inhibition of this miRNA augmented the expression of those genes. Mechanistically, miR-4734 was found to restrict the expression of the transcriptional activator NF-kappa-B inhibitor zeta (NFKBIZ), which is required for optimal expression of the proinflammatory genes and whose mRNA is targeted directly by miR-4734. Concordantly, overexpression of NFKBIZ compromised the effects of miR-4734, underscoring the importance of this direct targeting. As the effects of miR-4734 were evident under stress but not under basal conditions, it may possess therapeutic utility towards alleviating stress-induced pathologies.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
FEBS Lett
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Israel