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AMBRA1-mediated autophagy and apoptosis associated with an epithelial-mesenchymal transition in the development of cleft palate induced by all-trans retinoic acid.


ABSTRACT:

Background

Autophagy and apoptosis are involved in embryogenesis. However, little is known about the regulatory mechanism of AMBRA1-mediated autophagy and apoptosis associated with epithelial-mesenchymal transition (EMT) in the development of cleft palate (CP). This study is aimed to elucidate a novel regulatory mechanism by which AMBRA1 regulates autophagy and apoptosis associated with EMT during palatal fusion.

Methods

We performed lncRNA and mRNA co-expression profile analysis on embryonic gestation day 14.5 (E14.5) mouse embryos from control (n=3) and all-trans retinoic acid-treated (to induce cleft palate, n=3) C57BL/6J mice. Functional prediction for transcription factor (TF)-target gene relationship, which was obtained using Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analyses (GO/KEGG) pathway analysis, identified the regulatory "lncRNA-TF-target gene" using the trans model.

Results

The trans analysis revealed that some TFs (e.g., LEF1, SMAD4, and FOXD3) regulate lncRNA and gene expression. Finally, we identified a NONMMUT034790.2-LEF1-AMBRA1 trans-regulatory network associated with CP. Our results indicate that AMBRA1 might be a novel epigenetic biomarker in palatogenesis.

Conclusions

AMBRA1-mediated autophagy and apoptosis associated with EMT by a NONMMUT034790.2-LEF1-AMBRA1 trans-regulatory network might be an important mechanism underlying dysfunctional palatal fusion.

SUBMITTER: Shu X 

PROVIDER: S-EPMC6511560 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Publications

<i>AMBRA1</i>-mediated autophagy and apoptosis associated with an epithelial-mesenchymal transition in the development of cleft palate induced by all-trans retinoic acid.

Shu Xuan X   Dong Zejun Z   Shu Shenyou S  

Annals of translational medicine 20190401 7


<h4>Background</h4>Autophagy and apoptosis are involved in embryogenesis. However, little is known about the regulatory mechanism of <i>AMBRA1</i>-mediated autophagy and apoptosis associated with epithelial-mesenchymal transition (EMT) in the development of cleft palate (CP). This study is aimed to elucidate a novel regulatory mechanism by which <i>AMBRA1</i> regulates autophagy and apoptosis associated with EMT during palatal fusion.<h4>Methods</h4>We performed lncRNA and mRNA co-expression pro  ...[more]

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