METTL3 aggravates cell damage induced by Streptococcus pneumoniae via the NEAT1/CTCF/MUC19 axis

Dong-Bo Ma1, Hui Zhang1, Xi-Ling Wang1

  • 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, China.

Insights

Methyltransferase-like 3 (METTL3) exacerbates Streptococcus pneumoniae-induced lung injury by upregulating NEAT1, CTCF, and MUC19. Downregulating METTL3 alleviates apoptosis and inflammation in alveolar epithelial cells.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Immunology

Background:

  • Alveolar barrier disruption is a key factor in acute lung injury.
  • Streptococcus pneumoniae (SP) infection can lead to significant lung damage.

Purpose of the Study:

  • To investigate the role of methyltransferase-like 3 (METTL3) in SP-induced apoptosis and inflammation of alveolar epithelial cells (AECs).
  • To elucidate the molecular mechanism involving METTL3, NEAT1, CTCF, and MUC19 in SP-induced lung injury.

Main Methods:

  • AECs were cultured and infected with SP.
  • Gene and protein expression levels were analyzed using qRT-PCR, Western blot, and ELISA.
  • N6-methyladenosine (m6A) modification, NEAT1 subcellular localization, and NEAT1-CTCF binding were assessed.
  • Methylated RNA immunoprecipitation-qPCR was employed.

Main Results:

  • SP infection upregulated METTL3 expression and induced apoptosis and inflammation in AECs.
  • Downregulation of METTL3 reduced SP-induced apoptosis and inflammation.
  • METTL3-mediated m6A modification increased NEAT1, which promoted its binding with CTCF, facilitating MUC19 transcription.
  • Overexpression of NEAT1 or MUC19 exacerbated SP-induced cell damage.

Conclusions:

  • METTL3 plays a critical role in aggravating SP-induced lung injury.
  • The METTL3-NEAT1-CTCF-MUC19 axis is a novel pathway contributing to SP-induced apoptosis and inflammation in AECs.
  • Targeting the METTL3 pathway may offer a therapeutic strategy for acute lung injury caused by SP.

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