The important role of MDM2, RPL5, and TP53 in mycophenolic acid-induced cleft lip and palate

Abstract

Mycophenolate embryopathy (MPE) is a mycophenolic acid (MPA)-induced congenital malformation with distinctive symptoms. Cleft lip/palate (CLP) is one of the most common symptoms of MPE. The aim of this study was to screen and verify hub genes involved in MPA-induced CLP and to explore the potential molecular mechanisms underlying MPE.Overlapping genes related to MPA and CLP were obtained from the GeneCards database. These genes were further analyzed via bioinformatics. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis results were visualized with the Cytoscape ClueGO plug-in. Gene protein-protein interaction (PPI) networks were constructed based on data obtained from the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database.Overall, 58 genes related to MPA and CLP were identified. The genes most relevant to MPA-induced CLP included ABCB1, COL1A1, Rac1, TGFβ1, EDN1, and TP53, as well as the TP53-associated genes MDM2 and RPL5. GO analysis demonstrated gene enrichment regarding such terms as ear, mesenchymal, striated muscle, and ureteric development. KEGG analysis demonstrated gene enrichment in such pathways as the HIF-1 signaling pathway, glycosylphosphatidylinositol-anchor biosynthesis, the TNF signaling pathway, and hematopoietic stem cell development.Bioinformatic analysis was performed on the genes currently known to be associated with MPA-induced CLP pathogenesis. MPA-induced CLP is mediated by multiple ribosome stress related genes and pathways. MDM2, RPL5 and TP53 could be the main contributor in this pathogenesis, along with several other genes. ABCB1 polymorphism could be related to the probability of MPA-induced CLP.