LncRNA-NONMMUT100923.1 regulates mouse embryonic palatal shelf adhesion by sponging miR-200a-3p to modulate medial epithelial cell desmosome junction during palatogenesis

Cleft palate (CP) is a common neonatal craniofacial defect caused by the adhesion and fusion dysfunction of bilateral embryonic palatal shelf structures. Long non-coding RNA (lncRNA) is involved in CP formation with regulatory mechanism unknown. In this study, all-trans retinoic acid (ATRA) was used to induced cleft palate in embryonic mice as model group. The RNA-sequencing was performed to screen differentially expressed genes between the normal and model group on embryonic day 16.5, and the expression of LncRNA-NONMMUT100923.1 and miR-200a-3p, Cdsn was confirmed by RT-PCR and western blotting. Colony formation, CCK-8 and EDU assays were performed to measure cell proliferation and apoptosis on mouse embryonic palatal shelf (MEPS) epithelial cells in vitro. Fluorescence in situ hybridization (FISH) and dual luciferase activity assays was used to investigate the regulatory effect of LncRNA-NONMMUT100923.1 on miRNA and its target genes. Up-regulation of LncRNA-NONMMUT100923.1 and Cdsn while downregulation of miR-200a-3p was found in the model group. The sponging effects of LncRNA-NONMMUT100923 on miR-200a-3p and the target gene relations between Cdsn and miR-200a-3p was confirmed. Low expression of miR-200a-3p was related to the increased expressed levels of Cdsn and the proliferation of MEPS epithelial cells. Thus, a potential ceRNA regulatory network in which LncRNA-NONMMUT100923.1 regulates Cdsn expression by competitively binding to endogenous miR-200a-3p during palatogenesis, which may inhibit MEPS adhesion by preventing the disintegration of the desmosome junction in medial edge epithelium cells. These findings indicate the regulatory role of lncRNA and provides a potential direction for target gene therapy of CP.