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FEBS Lett ; 597(9): 1233-1245, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36445168

RESUMEN

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.


Asunto(s)
MicroARNs , Citocinas/genética , Citocinas/metabolismo , Estrés del Retículo Endoplásmico/genética , MicroARNs/genética , MicroARNs/metabolismo , Factores de Transcripción/metabolismo , Regulación hacia Arriba , Humanos
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