The miR-223/nuclear factor I-A Axis regulates inflammation and cellular functions in intestinal tissues with necrotizing enterocolitis
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Officially Accepted for Publication


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AbstractWe previously demonstrated that microRNA(miR)-223 is overexpressed in intestinal tissue of infants with necrotizing enterocolitis (NEC). The objective of the current study was to identify the target gene of miR-223 and to investigate the role of the miR-223/nuclear factor I-A (NFIA) axis in cellular functions that underpin the pathophysiology of NEC. The target gene of miR-223 was identified by in silico target prediction bioinformatics, luciferase assay and western blotting. We investigated downstream signals of miR-223 and cellular functions by overexpressing the miRNA in Caco-2 and FHs74 cells stimulated with lipopolyssacharide (LPS) or lipoteichoic acid (LTA). NFIA was identified as a target gene of miR-223. Overexpression of miR-223 significantly induced MYOM1 and inhibited NFIA and RGN in Caco-2 cells, whilst co-stimulation with LTA decreased expression of GNA11, MYLK and PRKCZ. Expression levels of GNA11, MYLK, IL-6, and IL-8 were increased and levels of NFIA and RGN were decreased in FHs74 cells. These potential downstream genes were significantly correlated with levels of miR-223 or NFIA in primary NEC tissues. Overexpression of miR-223 significantly increased apoptosis of Caco-2 and FHs74 cells, while proliferation of FHs74 was inhibited. These results suggest that upon binding with NFIA, miR-223 regulates functional effectors in pathways of apoptosis, cell proliferation, G-protein signaling, inflammation and smooth muscle contraction. The miR-223/NFIA axis may play an important role in the pathophysiology of NEC by enhancing inflammation and tissue damage.
Acceptance Date13/02/2021
All Author(s) ListWu YZ, Chan KYY, Leung KT, Lam HS, Tam YH, Lee KH, Li K, Ng PC
Journal nameFEBS Open Bio
Year2021
PublisherJohn Wiley & Sons, Inc
Place of PublicationOxford, UK
ISSN2211-5463
LanguagesEnglish-United Kingdom
KeywordsNFIA, apoptosis, cell proliferation, miR-223, necrotizing enterocolitis

Last updated on 2021-16-06 at 23:41