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

Xuan Shu,Hongqiu Cheng,Shenyou Shu

doi:10.1002/mgg3.522

Abstract

BackgroundIncreasing 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).MethodsC57BL/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.ResultsA 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.ConclusionsOur 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.

Highlights

Cleft palate (CP) is a common congenital birth defect in the oral and craniofacial region that results in feeding, speech, and hearing difficulties and occurs in approximately 1.7 in 1,000 live births worldwide (Mossey, et al, 2009)
The transcription factor (TF) that were significantly related to the long non‐coding RNAs (lncRNAs) were obtained, identifying the TF/chromatin regulatory factor that might be associated with lncRNAs
We investigated whether aberrant lncRNAs have potential effects on embryonic mouse palate shelf fusion during palatal fusion in all‐trans retinoic acid (ATRA)‐induced mouse cleft palate (CP)

Summary

Introduction

Cleft palate (CP) is a common congenital birth defect in the oral and craniofacial region that results in feeding, speech, and hearing difficulties and occurs in approximately 1.7 in 1,000 live births worldwide (Mossey, et al, 2009). It may originate from disruptions in epithelial–mesenchymal transition (EMT) of the medial edge epithelium (MEE) during palate shelf fusion, including an imbalance in MEE apoptosis, post‐fusion rupture, or failure of mesenchyme consolidation (Choi, et al 2011). A previous study showed that LEF1 (OMIM 153245) and SMAD7 (OMIM 602932) were involved in CP and palate formation (Mitra, et al, 2016; Nawshad, 2010; Rice, 2005; Thiery & Sleeman, 2006), but the underlying palatogenesis and potential regulatory mechanisms are still unclear.

Objectives

Findings

Discussion

Conclusion