| First Author | Sun Y | Year | 2021 |
| Journal | Cell Cycle | Volume | 20 |
| Issue | 22 | Pages | 2372-2386 |
| PubMed ID | 34779712 | Mgi Jnum | J:317397 |
| Mgi Id | MGI:6852706 | Doi | 10.1080/15384101.2021.1982506 |
| Citation | Sun Y, et al. (2021) 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 |
| abstractText | 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 beta-catenin, TCF4 and other related genes in the Wnt/beta-catenin signaling pathway.Collectively, these results demonstrated that miR-222-3p regulates the Wnt/beta-catenin signaling pathway through Ddit4 inhibition in HT-22 cells, resulted in cell proliferation and apoptosis imbalance, and thus led to neural tube defects. |
