A novel lncRNA-mediated trans-regulatory mechanism in the development of cleft palate in mouse

Increasing evidence indicates that long non-coding RNAs (lncRNAs) play crucial regulatory roles in epithelial-mesenchymal transition (EMT). However, the regulatory mechanisms during EMT of the medial edge epithelium (MEE) remain elusive. The aim of this work is to reveal a novel lncRNA-regulated dysfunction of EMT involved in the development of cleft palate (CP).

C57BL/6 J mice at embryonic gestation day 14.5 (n = 6, 3 case samples vs. 3 control samples) were used to establish the CP model for lncRNA-mRNA co-expression profile analysis after high-throughput sequencing. Functional predictions for the differentially expressed lncRNA-mRNA co-expression with transcription factor (TF)-target gene relationship Gene Ontology/Kyoto Encyclopedia of Genes and Genomes pathway (GO/KEGG) analyses identified the regulatory "lncRNA-TF-target gene" trans model.

A total of 583 differentially expressed lncRNAs and 703 differentially expressed mRNAs were identified. The results of trans analysis revealed that some TFs (LEF1, SMAD4, and FOXD3) regulate lncRNAs and gene expression. Finally, we identified the NONMMUT034790.2-LEF1-SMAD7 co-expression trans-regulatory network that might be associated with CP.

Our results revealed that NONMMUT034790.2 might be a novel epigenetic biomarker in CP. The integration of lncRNA modulators into trans-regulatory networks will further enhance our understanding of lncRNA functions and regulatory mechanisms during palatal fusion in ATRA-induced mouse CP.