DataSheet1_Crucial Roles of microRNA-16-5p and microRNA-27b-3p in Ameloblast Differentiation Through Regulation of Genes Associated With Amelogenesis Imperfecta.PDF

Amelogenesis imperfecta is a congenital disorder within a heterogeneous group of conditions characterized by enamel hypoplasia. Patients suffer from early tooth loss, social embarrassment, eating difficulties, and pain due to an abnormally thin, soft, fragile, and discolored enamel with poor aesthetics and functionality. The etiology of amelogenesis imperfecta is complicated by genetic interactions. To identify mouse amelogenesis imperfecta-related genes (mAIGenes) and their respective phenotypes, we conducted a systematic literature review and database search and found and curated 70 mAIGenes across all of the databases. Our pathway enrichment analysis indicated that these genes were enriched in tooth development-associated pathways, forming four distinct groups. To explore how these genes are regulated and affect the phenotype, we predicted microRNA (miRNA)-gene interaction pairs using our bioinformatics pipeline. Our miRNA regulatory network analysis pinpointed that miR-16-5p, miR-27b-3p, and miR-23a/b-3p were hub miRNAs. The function of these hub miRNAs was evaluated through ameloblast differentiation assays with/without the candidate miRNA mimics using cultured mouse ameloblast cells. Our results revealed that overexpression of miR-16-5p and miR-27b-3p, but not miR-23a/b-3p, significantly inhibited ameloblast differentiation through regulation of mAIGenes. Thus, our study shows that miR-16-5p and miR-27b-3p are candidate pathogenic miRNAs for amelogenesis imperfecta.

成釉不全症是一种先天性疾患，隶属于一组异质性疾病，其特征为釉质发育不良。患者常遭受早期牙齿脱落、社交尴尬、进食困难及因异常薄弱、柔软、脆弱且色泽不均的釉质所引起的疼痛，该釉质的美观与功能均受损。成釉不全症的病因复杂，由遗传相互作用所造成。为辨识与小鼠成釉不全症相关的基因（mAIGenes）及其相应的表型，我们进行了系统性的文献综述和数据库检索，并在所有数据库中筛选并整理了70个mAIGenes。我们的通路富集分析表明，这些基因在牙齿发育相关通路中富集，并形成了四个不同的组群。为探究这些基因的调控机制及其对表型的影响，我们利用生物信息学管道预测了miRNA（miRNA）-基因相互作用对。我们的miRNA调控网络分析精确地指出，miR-16-5p、miR-27b-3p和miR-23a/b-3p是核心miRNA。通过使用培养的小鼠成釉细胞进行带或不带候选miRNA模拟物的成釉细胞分化实验，我们评估了这些核心miRNA的功能。我们的研究结果显示，miR-16-5p和miR-27b-3p的高表达，而非miR-23a/b-3p，通过调节mAIGenes显著抑制了成釉细胞分化。因此，本研究表明miR-16-5p和miR-27b-3p是成釉不全症潜在的致病miRNA。