Iwaya Chihiro, Iwata Junichi
Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, MI, United States.
Department of Diagnostic & Biomedical Sciences, School of Dentistry, The University of Texas Health Science Center at Houston, Houston, TX, United States.
Front Cell Dev Biol. 2025 Jul 24;13:1587052. doi: 10.3389/fcell.2025.1587052. eCollection 2025.
Hypertelorism, characterized by an abnormal increase in the distance between the eyes, is often associated with various congenital birth defects. While there is increasing evidence suggesting common underlying mechanisms for hypertelorism, the role of microRNAs (miRNAs)-short noncoding RNAs that suppress target genes by inhibiting translation and degrading mRNA-in the condition's pathogenesis remains unclear. This study aimed to identify the miRNAs associated with hypertelorism in mice. By searching the Mouse Genome Informatics (MGI) database and reviewing full-text references, we identified a total of 31 genes potentially related to hypertelorism. Advanced bioinformatics analyses revealed nine miRNAs that may regulate these genes. We experimentally evaluated candidate miRNAs in assays of cell proliferation and target gene regulation in primary cells isolated from developing frontonasal process mouse embryonic frontonasal mesenchymal and O9-1 cells, a murine neural crest cell line. Our findings indicated that overexpression of either miR-383-3p or miR-6951-3p stimulated cell proliferation, whereas miR-7116-3p and miR-124-3p did not have this effect. Additionally, we confirmed that miR-383-3p and miR-6951-3p regulated the expression of a set of hypertelorism-related genes in a dose-dependent manner. These results suggest that miR-383-3p and miR-6951-3p play significant roles in the development of hypertelorism.
眼距过宽症的特征是两眼之间的距离异常增加,常与各种先天性出生缺陷相关。虽然越来越多的证据表明眼距过宽症存在共同的潜在机制,但微小RNA(miRNA)——通过抑制翻译和降解mRNA来抑制靶基因的短非编码RNA——在该病症发病机制中的作用仍不清楚。本研究旨在鉴定与小鼠眼距过宽症相关的miRNA。通过搜索小鼠基因组信息学(MGI)数据库并查阅全文参考文献,我们共鉴定出31个可能与眼距过宽症相关的基因。先进的生物信息学分析揭示了9种可能调控这些基因的miRNA。我们在从发育中的额鼻突小鼠胚胎额鼻间充质分离的原代细胞以及小鼠神经嵴细胞系O9-1细胞的细胞增殖和靶基因调控试验中对候选miRNA进行了实验评估。我们的研究结果表明,miR-383-3p或miR-6951-3p的过表达刺激细胞增殖,而miR-7116-3p和miR-124-3p则没有这种作用。此外,我们证实miR-383-3p和miR-6951-3p以剂量依赖的方式调控一组与眼距过宽症相关基因的表达。这些结果表明,miR-383-3p和miR-6951-3p在眼距过宽症的发展中起重要作用。
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