MicroRNA suppression of stress-responsive NDRG2 during dexamethasone treatment in skeletal muscle cells

MicroRNAs (miRNAs) are increasingly being identified as modulatory molecules for physiological and pathological processes in muscle. Here, we investigated whether miRNAs influenced the expression of the stress-responsive gene N-myc downstream-regulated gene 2 (Ndrg2) in skeletal muscle cells through the targeted degradation or translation inhibition of NDRG2 mRNA transcripts during basal or catabolic stress conditions.

These findings highlight modulatory and co-regulatory roles for miR-23a, -23b and -28 and their novel regulation of NDRG2 during stress conditions in muscle.

Three miRNAs, mmu-miR-23a-3p (miR-23a), mmu-miR-23b-3p (miR-23b) and mmu-miR-28-5p (miR-28), were identified using an in silico approach and confirmed to target the 3' untranslated region of the mouse Ndrg2 gene through luciferase reporter assays. However, miR-23a, -23b or -28 overexpression had no influence on NDRG2 mRNA or protein levels up to 48 h post treatment in mouse C2C12 myotubes under basal conditions. Interestingly, a compensatory decrease in the endogenous levels of the miRNAs in response to each other's overexpression was measured. Furthermore, dexamethasone, a catabolic stress agent that induces NDRG2 expression, decreased miR-23a and miR-23b endogenous levels at 24 h post treatment suggesting an interplay between these miRNAs and NDRG2 regulation under similar stress conditions. Accordingly, when overexpressed simultaneously, miR-23a, -23b and -28 attenuated the dexamethasone-induced increase of NDRG2 protein translation but did not affect Ndrg2 gene expression.