A role for miR-4734 in conditional suppression of ER stress-associated pro-inflammatory responses [starved vs control HFF]

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 pro-inflammatory cytokines and endoplasmic reticulum (ER) stress-associated genes. Conversely, inhibition of this miRNA augmented the expression of those genes. Mechanistically, miR-4734 was found to restrict the expression of NFKBIZ, that is required for optimal expression of the pro-inflammatory 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 this miR-4734 were evident under stress, but not under basal conditions, it may be considered as a therapeutic agent. For the mRNA expression array analysis (starved vs control HFF), total RNA derived from either control, 16 or 48 hours starved cells, each from 3 biological repeats, was used.