The miR‐223/nuclear factor I‐A axis regulates inflammation and cellular functions in intestinal tissues with necrotizing enterocolitis

Autor: Kathy Yuen Yee Chan, Yuk Him Tam, Yu Zheng Wu, Karen Li, Kim Hung Lee, Kam Tong Leung, Pak Cheung Ng, Hugh Simon Lam
Rok vydání: 2021
Předmět:
Zdroj: FEBS Open Bio
FEBS Open Bio, Vol 11, Iss 7, Pp 1907-1920 (2021)
ISSN: 2211-5463
DOI: 10.1002/2211-5463.13164
Popis: We 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 lipopolysaccharide 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, while costimulation 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.
MicroRNA (miR)‐223 is overexpressed in the bowel of infants with necrotizing enterocolitis (NEC). This study investigated the role of miR‐223 in cellular functions that underpin the pathophysiology of NEC. Through identifying direct and downstream targets, and using a gain‐of‐function approach, we demonstrated that the miR‐223/NFIA axis could regulate NEC pathophysiology by interacting with multiple pathways that aggravate inflammation and tissue damage.
Databáze: OpenAIRE
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