Giovannetti Agnese, Guarnieri Rosanna, Petrizzelli Francesco, Lazzari Sara, Padalino Gabriella, Traversa Alice, Napoli Alessandro, Di Giorgio Roberto, Pizzuti Antonio, Parisi Chiara, Mazza Tommaso, Barbato Ersilia, Caputo Viviana
Clinical Genomics Laboratory, Fondazione IRCCS Casa Sollievo della Sofferenza, S. Giovanni Rotondo (FG), Italy.
Department of Oral and Maxillofacial Sciences, School of Dentistry, Sapienza University of Rome, Rome, Italy.
J Dent Sci. 2024 Oct;19(4):2150-2156. doi: 10.1016/j.jds.2024.03.013. Epub 2024 Mar 22.
BACKGROUND/PURPOSE: Tooth development, or odontogenesis, is a complex process in which several molecular pathways play a key role. Recently, microRNAs, a class of approximately 20-nucleotide small RNA molecules that regulate gene expression, have been implicated in the odontogenesis process. This study aimed to assess the role of miRNAs in odontogenesis anomalies, specifically agenesis and impaction.
We analyzed a manually curated list of 82 miRNAs associated with human odontogenesis, sourced from literature data. Employing two different approaches to validate findings, we conducted functional enrichment analysis to evaluate the cell pathways, diseases, and phenotypes enriched for those miRNAs.
Our findings indicate that the analyzed miRNAs regulate pathways linked to tooth anomalies, including the TGFꞵ and Wnt signaling pathways, and those governing the pluripotency of stem cells, known to mediate various cellular processes, and interconnected with odontogenesis-related pathways. Furthermore, the analysis disclosed several pathways associated with tumors, including small cell lung and gastric cancer. These results were confirmed also by diseases and phenotypes enrichment evaluation. Moreover, cell network analysis disclosed that miRNAs are embedded and interconnected in networks associated with dental diseases and cancer development, thus confirming the functional enrichment analyses.
In summary, our results offer a quantitative measure of the potential involvement of miRNAs in regulating pathways crucial for developmental processes, notably odontogenesis, and provide results suggesting potential association with oncogenesis processes as well.
背景/目的：牙齿发育，即牙发生，是一个复杂的过程，其中几个分子途径起着关键作用。最近，微小RNA（一类调节基因表达的约20个核苷酸的小RNA分子）已被证明参与牙发生过程。本研究旨在评估微小RNA在牙发生异常，特别是牙缺失和牙阻生中的作用。
我们分析了一份从文献数据中手动整理的与人类牙发生相关的82种微小RNA列表。采用两种不同的方法来验证研究结果，我们进行了功能富集分析，以评估这些微小RNA所富集的细胞途径、疾病和表型。
我们的研究结果表明，所分析的微小RNA调节与牙齿异常相关的途径，包括TGFꞵ和Wnt信号通路，以及那些控制干细胞多能性的途径，已知这些途径介导各种细胞过程，并与牙发生相关途径相互关联。此外，分析还揭示了几种与肿瘤相关的途径，包括小细胞肺癌和胃癌。疾病和表型富集评估也证实了这些结果。此外，细胞网络分析表明，微小RNA嵌入并相互连接在与牙科疾病和癌症发展相关的网络中，从而证实了功能富集分析。
总之，我们的结果提供了一种定量方法，来衡量微小RNA在调节对发育过程（特别是牙发生）至关重要的途径中的潜在参与程度，并提供了表明其与肿瘤发生过程也可能相关的结果。
