miR-222-3p is involved in neural tube closure by directly targeting Ddit4 in RA induced NTDs mouse model.
Cell Cycle
; 20(22): 2372-2386, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-34779712
ABSTRACT
Previously our results showed miR-222-3p was significantly downregulated in retinoic acid-induced neural tube defect (NTD) mouse model through transcriptome. Down-regulation of miR-222-3p may be a causative biomarker in NTDs. In this study, RNA was extracted from mouse embryos at E8.5, E9.5 and E10.5, and the expression level of miR-222-3p was measured by quantitative real-time PCR analysis. The preliminary mechanism of miR-222-3p in NTDs involved in cell proliferation, apoptosis and migration was investigated in mouse HT-22 cell line. The expression of miR-222-3p was significantly decreased at E8.5, E9.5 and E10.5 developed in mouse embryos which were consistent with our transcriptome sequencing. Suppression of miR-222-3p in HT-22 cells resulted in the inhibition of cell proliferation and migration, cell cycle and apoptosis. Moreover, DNA damage transcript 4 (Ddit4) was identified as a direct and functional target of miR-222-3p. miR-222-3p is negatively regulated by Ddit4. The mutation of binding site of Ddit4 3'UTR abrogated the responsiveness of luciferase reporters to miR-222-3p and showed that Ddit4 expression partially attenuated the function of miR-222-3p. We preliminatively confirmed that low expression of miR-222-3p has reduced the expression of ß-catenin, TCF4 and other related genes in the Wnt/ß-catenin signaling pathway.Collectively, these results demonstrated that miR-222-3p regulates the Wnt/ß-catenin signaling pathway through Ddit4 inhibition in HT-22 cells, resulted in cell proliferation and apoptosis imbalance, and thus led to neural tube defects.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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MicroRNAs
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Defeitos do Tubo Neural
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Cell Cycle
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China