Mycophenolate mofetil reduces cell viability associated with the miR-205-PAX9 pathway in human lip fibroblast cells.

Cleft lip is a birth defect associated with environmental and genetic factors. Recently, microRNAs (miRNAs) have been reported to play a crucial role in lip formation, with the disruption of miRNAs influencing the development of cleft lip. Exposure to medicinal agents in pregnant women is one of the reasons for cleft lip. Although an association between pharmaceuticals-induced cleft lip and miRNAs has been suggested, it remains to be fully elucidated. This study aimed to clarify the molecular mechanism of mycophenolate mofetil (MPM)-induced inhibition of cell proliferation and miRNA expression in human lip fibroblast (KD) cells. Cell viability, apoptosis, and cell cycle-related markers were evaluated after 72 h of MPM treatment. In addition, miRNA levels and the expression of their downstream genes were measured, and a rescue experiment was performed by overexpressing PAX9. We showed that MPM dose-dependently reduced the viability of KD cells. In addition, MPM treatment suppressed cyclin-D1 and cyclin dependent kinase-6 expression in KD cells. Furthermore, MPM upregulated miR-205 expression and downregulated the expression of PAX9 (downstream gene). Moreover, PAX9 overexpression alleviated MPM-induced inhibition of cell proliferation. These results suggest that MPM suppresses cell viability by modulating miR-205-PAX9 expression.