Cleft Palate Induced by Mycophenolate Mofetil Is Associated with miR-4680-3p and let-7c-5p in Human Palate Cells

<b>Background/Objectives</b>: Cleft palate is a birth defect associated with environmental and genetic factors. Disturbance of microRNAs (miRNAs) and exposure to medicinal agents during pregnancy can cause cleft palate. Although an association between medicine-induced cleft palate and miRNAs has been suggested, it remains to be fully elucidated. This study aimed to clarify the molecular mechanism underlying mycophenolate mofetil (MPM)-induced inhibition of cell proliferation and miRNA expression in human embryonic palatal mesenchymal (HEPM) cells. <b>Methods</b>: Cell viability, apoptosis, and cell cycle-related markers were evaluated 48 h after MPM treatment. In addition, miRNA levels and expression of their downstream genes were measured, and a rescue experiment was performed using <i>miR-4680-3p</i> and/or <i>let-7c-5p</i> inhibitors. <b>Results</b>: MPM dose-dependently reduced HEPM cell viability. Additionally, MPM treatment suppressed cyclin-D1, cyclin E1, cyclin-dependent kinase (CDK)-2, and CDK6 expression in HEPM cells. Furthermore, MPM upregulated <i>miR-4680-3p</i> and <i>let-7c-5p</i> expression and downregulated the downstream genes of each miRNA. Moreover, <i>miR-4680-3p</i> and/or <i>let-7c-5p</i> inhibitors alleviated MPM-induced inhibition of cell proliferation. <b>Conclusions</b>: These results suggest that MPM-induced cleft palate is associated with <i>miR-4680-3p</i> and <i>let-7c-5p</i> expression in HEPM cells.