Dataset Information

MiR-322 treatment rescues cell apoptosis and neural tube defect formation through silencing NADPH oxidase 4.

ABSTRACT:

Aims

Failure of neural tube closure resulting from excessive apoptosis leads to neural tube defects (NTDs). NADPH oxidase 4 (NOX4) is a critical mediator of cell growth and death, yet its role in NTDs has never been characterized. NOX4 is a potential target of miR-322, and we have previously demonstrated that miR-322 was involved in high glucose-induced NTDs. In this study, we investigated the effect of NOX4 on the embryonic neuroepithelium in NTDs and reveal a new regulatory mechanism for miR-322 that disrupts neurulation by ameliorating cell apoptosis.

Methods

All-trans-retinoic acid (ATRA)-induced mouse model was utilized to study NTDs. RNA pull-down and dual-luciferase reporter assays were used to confirm the interaction between NOX4 and miR-322. In mouse neural stem cells and whole-embryo culture, Western blot and TUNEL were carried out to investigate the effects of miR-322 and NOX4 on neuroepithelium apoptosis in NTD formation.

Results

NOX4, as a novel target of miR-322, was upregulated in ATRA-induced mouse model of NTDs. In mouse neural stem cells, the expression of NOX4 was inhibited by miR-322; still further, NOX4-triggered apoptosis was also suppressed by miR-322. Moreover, in whole-embryo culture, injection of the miR-322 mimic into the amniotic cavity attenuated cell apoptosis in NTD formation by silencing NOX4.

Conclusion

miR-322/NOX4 plays a crucial role in apoptosis-induced NTD formation, which may provide a new understanding of the mechanism of embryonic NTDs and a basis for potential therapeutic target against NTDs.

SUBMITTER: Liu YS

PROVIDER: S-EPMC7415201 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Publications

miR-322 treatment rescues cell apoptosis and neural tube defect formation through silencing NADPH oxidase 4.

Liu Yu-Si YS Gu Hui H Huang Tian-Chu TC Wei Xiao-Wei XW Ma Wei W Liu Dan D He Yi-Wen YW Luo Wen-Ting WT Huang Jie-Ting JT Zhao Duan D Jia Shan-Shan SS Wang Fang F Zhang Ting T Bai Yu-Zuo YZ Wang Wei-Lin WL Yuan Zheng-Wei ZW

CNS neuroscience & therapeutics 20200424 9

<h4>Aims</h4>Failure of neural tube closure resulting from excessive apoptosis leads to neural tube defects (NTDs). NADPH oxidase 4 (NOX4) is a critical mediator of cell growth and death, yet its role in NTDs has never been characterized. NOX4 is a potential target of miR-322, and we have previously demonstrated that miR-322 was involved in high glucose-induced NTDs. In this study, we investigated the effect of NOX4 on the embryonic neuroepithelium in NTDs and reveal a new regulatory mechanism f ...[more]

PMID: 32329577

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