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The m6A methyltransferase METTL3 affects cell proliferation and migration by regulating YAP expression in

Zhaorong Huang1, Caiyun Luo1, Xinwei Hou1

  • 1Department of Pediatric Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, Guangdong, China.

Pediatric Surgery International
|February 15, 2023
PubMed
Abstract

Insights

Methyltransferase-like 3 (METTL3) dysregulation is linked to Hirschsprung disease (HSCR). METTL3 impacts neural crest cell growth and migration by regulating YAP, suggesting a role in HSCR pathogenesis.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Genetics

Background:

  • METTL3 (methyltransferase-like 3) is crucial for mRNA metabolism, including stability, splicing, and translation.
  • Its role in Hirschsprung disease (HSCR), a congenital disorder, is not well understood.
  • This study investigates METTL3's involvement and molecular mechanisms in HSCR development.

Purpose of the Study:

  • To elucidate the role of METTL3 in Hirschsprung disease (HSCR).
  • To identify the molecular mechanism by which METTL3 influences HSCR pathogenesis.
  • To investigate the relationship between METTL3 and YAP in HSCR.

Main Methods:

  • Gene and protein expression analysis (RT-qPCR, Western blot, immunohistochemistry).
  • Assessment of cell proliferation and migration (CCK-8, Transwell assays).
  • Quantification of m6A modification levels using colorimetry.

Main Results:

  • Reduced m6A levels were observed in stenotic HSCR intestinal tissue.
  • METTL3 knockdown inhibited cell proliferation and migration, decreased m6A levels, and increased YAP expression.
  • A negative correlation between YAP and METTL3 expression was found in cell lines and HSCR tissue.

Conclusions:

  • METTL3 interacts with YAP in the context of HSCR.
  • METTL3 regulates neural crest cell proliferation and migration upstream of YAP.
  • METTL3 is implicated in the pathogenesis of HSCR.
Keywords:
Hirschsprung disease (HSCR)METTL3MethyltransferaseNeural crest cellsYAPm6A

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