Critical microRNAs and regulatory motifs in cleft palate identified by a conserved miRNA-TF-gene network approach in humans and mice.

Critical microRNAs and regulatory motifs in cleft palate identified by a conserved miRNA-TF-gene network approach in humans and mice. Brief Bioinform. 2019 Oct 07;: Authors: Li A, Jia P, Mallik S, Fei R, Yoshioka H, Suzuki A, Iwata J, Zhao Z Abstract Cleft palate (CP) is the second most common congenital birth defect. The etiology of CP is complicated, with involvement of various genetic and environmental factors. To investigate the gene regulatory mechanisms, we designed a powerful regulatory analytical approach to identify the conserved regulatory networks in humans and mice, from which we identified critical microRNAs (miRNAs), target genes and regulatory motifs (miRNA-TF-gene) related to CP. Using our manually curated genes and miRNAs with evidence in CP in humans and mice, we constructed miRNA and transcription factor (TF) co-regulation networks for both humans and mice. A consensus regulatory loop (miR17/miR20a-FOXE1-PDGFRA) and eight miRNAs (miR-140, miR-17, miR-18a, miR-19a, miR-19b, miR-20a, miR-451a and miR-92a) were discovered in both humans and mice. The role of miR-140, which had the strongest association with CP, was investigated in both human and mouse palate cells. The overexpression of miR-140-5p, but not miR-140-3p, significantly inhibited cell proliferation. We further examined whether miR-140 overexpression could suppress the expression of its predicted target genes (BMP2, FGF9, PAX9 and PDGFRA). Our results indic...
Source: Briefings in Bioinformatics - Category: Bioinformatics Authors: Tags: Brief Bioinform Source Type: research