Faculty, Staff and Student Publications
Language
English
Publication Date
7-15-2020
Journal
Briefings in Bioinformatics
DOI
10.1093/bib/bbz082
PMID
31589286
PMCID
PMC7412957
PubMedCentral® Posted Date
10-7-2019
PubMedCentral® Full Text Version
Post-print
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 indicated that miR-140-5p overexpression suppressed the expression of BMP2 and FGF9 in cultured human palate cells and Fgf9 and Pdgfra in cultured mouse palate cells. In summary, our conserved miRNA-TF-gene regulatory network approach is effective in detecting consensus miRNAs, motifs, and regulatory mechanisms in human and mouse CP.
Keywords
Animals, Cleft Palate, Conserved Sequence, Gene Regulatory Networks, Humans, Mice, MicroRNAs, Transcription Factors
Published Open-Access
yes
Recommended Citation
, "Critical microRNAs and Regulatory Motifs in Cleft Palate Identified by a Conserved miRNA-TF-Gene Network Approach in Humans and Mice" (2020). Faculty, Staff and Student Publications. 73.
https://digitalcommons.library.tmc.edu/uthdb_docs/73