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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\u2013TF\u2013gene) 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\u2013FOXE1\u2013PDGFRA) 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\u2013TF\u2013gene regulatory network approach is effective in detecting consensus miRNAs, motifs, and regulatory mechanisms in human and mouse CP.<\/jats:p>","DOI":"10.1093\/bib\/bbz082","type":"journal-article","created":{"date-parts":[[2019,6,17]],"date-time":"2019-06-17T11:08:41Z","timestamp":1560769721000},"page":"1465-1478","source":"Crossref","is-referenced-by-count":37,"title":["Critical microRNAs and regulatory motifs in cleft palate identified by a conserved miRNA\u2013TF\u2013gene network approach in humans and mice"],"prefix":"10.1093","volume":"21","author":[{"given":"Aimin","family":"Li","sequence":"first","affiliation":[{"name":"Shaanxi Key Laboratory for Network Computing and Security Technology, School of Computer Science and Engineering, Xi'an University of Technology, Xi'an, Shaanxi, 710048, China"},{"name":"Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peilin","family":"Jia","sequence":"additional","affiliation":[{"name":"Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurav","family":"Mallik","sequence":"additional","affiliation":[{"name":"Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Fei","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory for Network Computing and Security Technology, School of Computer Science and Engineering, Xi'an University of Technology, Xi'an, Shaanxi, 710048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0977-434X","authenticated-orcid":false,"given":"Hiroki","family":"Yoshioka","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Biomedical Sciences, School of Dentistry, The University of Texas Health Science Center at Houston, Houston, TX 77054, USA"},{"name":"Center for Craniofacial Research, University of Texas Health Science Center at Houston, Houston, TX 77054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Biomedical Sciences, School of Dentistry, The University of Texas Health Science Center at Houston, Houston, TX 77054, USA"},{"name":"Center for Craniofacial Research, University of Texas Health Science Center at Houston, Houston, TX 77054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Iwata","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Biomedical Sciences, School of Dentistry, The University of Texas Health Science Center at Houston, Houston, TX 77054, USA"},{"name":"Center for Craniofacial Research, University of Texas Health Science Center at Houston, Houston, TX 77054, USA"},{"name":"MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3477-0914","authenticated-orcid":false,"given":"Zhongming","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA"},{"name":"MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, 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