2. Academic Validation
  3. Ethionine-mediated reduction of S-adenosylmethionine is responsible for the neural tube defects in the developing mouse embryo-mediated m6A modification and is involved in neural tube defects via modulating Wnt/β-catenin signaling pathway

Ethionine-mediated reduction of S-adenosylmethionine is responsible for the neural tube defects in the developing mouse embryo-mediated m6A modification and is involved in neural tube defects via modulating Wnt/β-catenin signaling pathway

  • Epigenetics Chromatin. 2021 Dec 4;14(1):52. doi: 10.1186/s13072-021-00426-3.
Li Zhang 1 2 3,  Rui Cao 1 4,  Dandan Li 1,  Yuqing Sun 2 3,  Juan Zhang 1,  Xiuwei Wang 5,  Ajab Khan 1,  Zhizhen Liu 1,  Bo Niu 6,  Jun Xu 7 8,  Jun Xie 9
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
  • 2 Department of Hepatobiliary and Pancreatic Surgery, First Clinical Medical College, Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
  • 3 Institute of Liver Diseases and Organ Transplantation, Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
  • 4 Biology Institute of Shanxi, Taiyuan, 030001, Shanxi, China.
  • 5 Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, China.
  • 6 Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, 030001, Shanxi, China. niub2004@126.com.
  • 7 Department of Hepatobiliary and Pancreatic Surgery, First Clinical Medical College, Shanxi Medical University, Taiyuan, 030001, Shanxi, China. junxutytg@163.com.
  • 8 Institute of Liver Diseases and Organ Transplantation, Shanxi Medical University, Taiyuan, 030001, Shanxi, China. junxutytg@163.com.
  • 9 Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, 030001, Shanxi, China. junxie@sxmu.edu.cn.
PMID: 34863249 DOI: 10.1186/s13072-021-00426-3
Abstract

Neural tube defects (NTDs) remain one of the most life-threatening birth defects affecting infants. Most patients with NTDs eventually develop lifelong disability, which cause significant morbidity and mortality and seriously reduce the quality of life. Our previous study has found that ethionine inhibits cell viability by disrupting the balance between proliferation and Apoptosis, and preventing neural stem cells from differentiating into neurons and astrocytes. However, how ethionine participates in the pathogenesis of neural tube development through N6-methyladenosine (m6A) modification remains unknown. This study aims to investigate METTL3- and ALKBH5-mediated m6A modification function and mechanism in NTDs. Herein, our results demonstrate that SAM play not only a compensatory role, it also leads to changes of m6A modification in neural tube development and regulation. Additionally, these data implicate that METTL3 is enriched in HT-22 cells, and METTL3 knockdown reduces cell proliferation and increases Apoptosis through suppressing Wnt/β-catenin signaling pathway. Significantly, overexpression of ALKBH5 can only inhibit cell proliferation, but cannot promote cell Apoptosis. This research reveals an important role of SAM in development of NTDs, providing a good theoretical basis for further research on NTDs. This finding represents a novel epigenetic mechanism underlying that the m6A modification has profound and lasting implications for neural tube development.

Keywords

Ethionine; M6A modification; METTL3; Neural tube defects; S-Adenosylmethionine; Wnt/β-catenin signaling pathway.

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