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

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journal contribution
posted on 28.05.2019, 00:00 authored by Bilal Ahmad Mir, Rabia Islam, Ming Kalanon, Aaron RussellAaron Russell, Victoria Foletta
BACKGROUND: 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. RESULTS: 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. CONCLUSION: 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.

History

Journal

BMC molecular and cell biology

Volume

20

Issue

1

Article number

12

Publisher

BioMed Central

Location

London, Eng.

ISSN

2661-8850

eISSN

2661-8850

Language

eng

Publication classification

C1 Refereed article in a scholarly journal

Copyright notice

2019, The Authors