부산대학교 도서관

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. [ABSTRACT FROM AUTHOR]