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miR-4734 conditionally suppresses ER stress-associated proinflammatory responses.
- Source :
-
FEBS letters [FEBS Lett] 2023 May; Vol. 597 (9), pp. 1233-1245. Date of Electronic Publication: 2022 Dec 11. - Publication Year :
- 2023
-
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.<br /> (© 2022 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
Details
- Language :
- English
- ISSN :
- 1873-3468
- Volume :
- 597
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- FEBS letters
- Publication Type :
- Academic Journal
- Accession number :
- 36445168
- Full Text :
- https://doi.org/10.1002/1873-3468.14548