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Dysregulation of miR‐431 and target gene FOXA1 in intestinal tissues of infants with necrotizing enterocolitis
Author(s) -
Wu Yu Zheng,
Chan Kathy Yuen Yee,
Leung Kam Tong,
Lam Hugh Simon,
Tam Yuk Him,
Lee Kim Hung,
Li Karen,
Ng Pak Cheung
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201801470r
Subject(s) - foxa1 , apoptosis , proinflammatory cytokine , lipoteichoic acid , microrna , biology , necrotizing enterocolitis , lgr5 , cancer research , microbiology and biotechnology , immunology , gene expression , inflammation , gene , signal transduction , medicine , wnt signaling pathway , genetics , bacteria , staphylococcus aureus
The level of microRNA (miR)‐431 was found to be markedly up‐regulated in intestinal tissue of necrotizing enterocolitis (NEC). The objective of this study was to identify the target gene of miR‐431 and to investigate the role of the miR‐431‐FOXA1 axis in the pathophysiology of NEC. The target gene of miR‐431 was identified by in silico target prediction bioinformatics, luciferase assay, and Western blotting. Effects of miR‐431 on downstream expression signals, cell proliferation, and apoptosis were investigated by overexpression in Caco‐2 cells upon stimulation by LPS or lipoteichoic acid (LTA). FOXA1 was identified as the target gene of miR‐431. Overexpression of miR‐431 in Caco‐2 cells significantly inhibited FOXA1, ESRRG , and HNF4A and activated IL‐6, LGR5, NFKB2, PLA2G2A, PRKCZ , and TNF. IL‐8 and ‐10 were enhanced when costimulated with LPS or LTA. These potential downstream genes were also significantly dysregulated in primary NEC tissues compared with surgical‐control tissues. Overexpression of miR‐431 significantly decreased proliferation and increased apoptosis of Caco‐2 cells. A proposed network of miR‐431‐FOXA1 interaction with LPS and LTA receptors demonstrates dysregulation of transcription factors, inflammatory mediators, epithelium tight junction regulators, and cell proliferation and apoptosis signals. The miR‐431‐FOXA1 axis could in part be responsible for the intensification of the inflammatory response in NEC tissues and contribute to the proinflammatory pathophysiology.—Wu, Y. Z., Chan, K. Y. Y., Leung, K. T., Lam, H. S., Tam, Y. H., Lee, K. H., Li, K., Ng, P. C. Dysregulation of miR‐431 and target gene FOXA1 in intestinal tissues of infants with necrotizing enterocolitis. FASEB J. 33, 5143–5152 (2019). www.fasebj.org