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.

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.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study did not receive any funding

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Institute Ethics committee, Institute of Science, BHU, Varanasi

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Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

All data produced in the present study are available upon reasonable request to the authors

AbbreviationsCTACongenital Tooth AgenesisWESWhole Exome SequencingDGEDifferential Gene ExpressionEOCEpithelial Ovarian CancerHCCHepatocellular CarcinomaOSCCOral Squamous Cell CarcinomaOCOvarian CancerB-CLLB-cell Chronic Lymphocytic LeukemiaAPLAcute Promyelocytic LeukemiaCCColorectal CancerASDAutism Spectrum DisorderMMMultiple MyelomaHNSCCHead and Neck Squamous Cell CarcinomaPDACPancreatic Ductal AdenocarcinomaDMDermatomyositisDMDDuchenne Muscular DystrophyFSHDFacioscapulohumeral Muscular DystrophyLGMD2ALimb-Girdle Muscular Dystrophies Types 2ANMNemaline MyopathyALLAcute Lymphoblastic LeukemiaPBCPrimary Biliary CirrhosisCLLChronic Lymphocytic LeukemiaATCAnaplastic Thyroid CarcinomaNAFLDNon-Alcoholic Fatty Liver Disease