Dysregulation of miR‐431 and target gene FOXA1 in intestinal tissues of infants with necrotizing enterocolitis
| Autor: | Kathy Yuen Yee Chan, Pak Cheung Ng, Yuk Him Tam, Karen Li, Kim Hung Lee, Yu Zheng Wu, Hugh Simon Lam, Kam Tong Leung |
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| Rok vydání: | 2019 |
| Předmět: |
Hepatocyte Nuclear Factor 3-alpha
Lipopolysaccharides 0301 basic medicine Enterocyte Blotting Western Apoptosis Real-Time Polymerase Chain Reaction Biochemistry 03 medical and health sciences 0302 clinical medicine Enterocolitis Necrotizing microRNA Genetics medicine Humans Intestinal Mucosa Molecular Biology Cell Proliferation business.industry Flow Cytometry medicine.disease digestive system diseases Teichoic Acids MicroRNAs HEK293 Cells 030104 developmental biology medicine.anatomical_structure Necrotizing enterocolitis Cancer research Caco-2 Cells Target gene FOXA1 business 030217 neurology & neurosurgery Plasmids Biotechnology |
| Zdroj: | The FASEB Journal. 33:5143-5152 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.201801470r |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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