Host: The Japanese Society of Toxicology
Name : The 51st Annual Meeting of the Japanese Society of Toxicology
Date : July 03, 2024 - July 05, 2024
Cleft palate (CP) is one of the most common birth defects worldwide (affects approximately 1:500 live births). The etiology of CP is multifactorial and involves environmental and genetic factors; for example, disruption of signaling pathways by gene mutation induce CP. Environmental factors such as medication usage, cigarette smoking, and alcohol consumption are well-known risk factors for CP since they lead to suppression of the expression of specific genes or signaling pathways. Although novel gene mutations associated with CP have been reported, it remains unclear how environmental and genetic factors affect CP.
MicroRNAs (miRNAs) are small endogenous RNA (18–24 nucleotides long) that regulate post-transcriptional gene expression. Recent studies suggested that miRNAs play crucial roles in palate development in human and mice. However, it is still unclear how and which miRNAs play important roles in CP.
To address this black box, I searched the miRNAs associated with mouse and human CP by combination with systematic review, bioinformatics, and cell proliferation assays. Using above combination test, I identified several miRNAs associated with CP both in human and mice. Additionally, I demonstrated that medicine (all-trans retinoic acid, phenobarbital)-induced CP induced specific miRNAs and miRNA inhibitor restored medicine-induced toxicity. The understanding of miRNA dysregulation by medicine will shed light on the link between environmental factor and genetic factor in CP.