Identification of Genes and microRNAs Associated with Midfacial Hypoplasia in Mice

Midfacial hypoplasia is a developmental defect caused by insufficient growth of the nasal placodes and maxillary prominences. While genetic studies in mice have identified key genes involved in midfacial development, the regulation of these genes during craniofacial development remains poorly understood. In this study, we demonstrate that microRNAs, short non-coding RNAs, play a crucial role in regulating genes involved in midfacial development. We identified 224 genes associated with midfacial malformations in mice. Through bioinformatics analyses, we predicted that several microRNAs, specifically miR-129-5p, miR-381-3p, miR-124-3p, miR-136-5p, miR-448-3p, miR-374, miR-96, and miR-882, could regulate the expression of these genes. Among these, we experimentally focused on the top four candidate microRNAs: miR-129-5p, miR-381-3p, miR-124-3p, and miR-136-5p. Our findings revealed that the overexpression of these microRNAs inhibited cell proliferation and osteogenesis in nasal process mesenchymal cells. These microRNAs regulated genes associated with midfacial malformations in a dose-dependent manner. Taken together, our results emphasize the significance of pathogenic microRNA–gene networks in the cause of midfacial malformations.