关键词: 先天性巨结肠； ChEA 3数据库； 转录因子； FOXP2基因

Abstract: Objective To explore the transcription factors involved in the development of the enteric nervous system and the pathogenesis of Hirschsprung disease (HSCR). Methods The ChEA 3 database was used to do analysis of prediction and enrichment of the target transcription factors that regulate the expression of HSCR susceptibility genes. The GeneMANIA online tool was utilized to construct a protein-protein interaction network diagram between transcription factors and target genes for exploration of their possible regulatory molecular pathways. Human Protein Atlas database was used to locate the protein expression of transcription factors and explores their expression in the nervous system and colon. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to verify the expression differences of related transcription factors in the stenotic and dilated bowel specimens of 30 children with HSCR. Results The ChEA 3 database was used to analyze prediction and enrichment of the transcription factors of 119 reported HSCR susceptibility genes, and it was found that FOXP2 can target 46 of them. Analysis in the GeneMANIA database shows that FOXP2 may regulate the expression of multiple HSCR susceptibility genes, co-expression with GLI 3 of the Hedgehog pathway, and genetic interaction with PTCH 1 . Human protein Atlas database analysis shows that FOXP 2 protein is highly expressed in brain neuronal cells and colon tissues. The median age of 30 children ( 23 boys and 7 girls) with HSCR was 1 year. The qRT-PCR results showed that the expression of FOXP2 mRNA in pathological tissues was lower than that in adjacent normal tissues, and the difference was statistically significant (t= 5 . 82 , P< 0 . 0001 ). Conclusions FOXP2 may influence the development of intestinal nerve cells through the regulation of Hedgehog signaling pathway, and thus contribute to the pathogenesis of HSCR.

Key words: Hirschsprung disease; ChEA 3 database; transcription factors; FOXP2 gene