Understanding Tooth Agenesis: A Multi-omics Insight into MicroRNA Regulation

Abstract

This study reveals novel microRNAs (miRNAs) implicated in congenital tooth agenesis (CTA), a common dental anomaly with a complex genetic basis. Through a multi-omics approach combining bioinformatics, whole exome sequencing, metabolite analysis, and gene expression profiling, we identified eight key miRNAs potentially involved in tooth development. Among these, four miRNAs viz. miR-218-5p, miR-15b-5p, miR-200b-3p, and let-7a-3p were validated as significant regulators in CTA, marking their first investigation in blood samples from CTA patients. Our analysis revealed that these miRNAs play critical roles in odontogenesis, influencing essential signaling pathways, including Wnt, FGF, and PI3 kinase pathways. Among these four, miR-218-5p and let-7a-3p emerged as key players in dental tissue morphogenesis, each contributing to previously unidentified networks crucial for tooth development.