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

Abstract

AbstractThis 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, includingWnt, FGF, andPI3kinase 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.This study highlights the potential of these miRNAs as non-invasive biomarkers for early CTA diagnosis and therapeutic targets. This is the first comprehensive investigation of these specific miRNAs in CTA, utilizing a multi-omics approach to offer fresh insights into miRNA-mediated mechanisms and their role in regulating dental anomalies. Our findings not only advance the understanding of the genetic regulation of tooth development but also pave the way for personalized approaches in managing dental anomalies. Further research is needed to validate these results and explore their clinical applications.Graphical Abstract