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METTL14-mediated m6A modification of DDIT4 promotes its mRNA stability in aging-related idiopathic pulmonary fibrosis

Dan Li1,2, Li Qian2, Yufeng Du2

  • 1First Clinical Medical College, Shanxi Medical University, Taiyuan, China.

Epigenetics
|February 7, 2025
PubMed

Insights

N6-methyladenosine (m6A) modification is altered in idiopathic pulmonary fibrosis (IPF). Downregulation of METTL14 impacts DDIT4 expression, suggesting a role in lung fibrosis pathogenesis.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Pulmonary Medicine

Background:

  • N6-methyladenosine (m6A) is implicated in fibrotic processes, but its role in aging-related idiopathic pulmonary fibrosis (IPF) is not well understood.
  • Investigating m6A modification mechanisms in IPF is crucial for understanding disease pathogenesis.

Purpose of the Study:

  • To elucidate the role and mechanism of m6A modification in aging-related IPF.
  • To identify key m6A regulators and target genes involved in IPF.

Main Methods:

  • MeRIP-seq and RNA-seq were used to analyze differential m6A modification and gene expression in IPF patients and controls.
  • MeRIP-qPCR and real-time PCR validated key findings.
  • Animal and cellular senescence models were employed to explore molecular mechanisms.

Main Results:

  • IPF lungs showed significant alterations in m6A peaks, with more decreased than increased peaks.
  • 749 differentially expressed genes (DEGs) were found to be affected by m6A methylation in IPF.
  • The m6A regulator METTL14 was downregulated in IPF, correlating with decreased m6A modification and increased mRNA/protein levels of DDIT4, a gene implicated in alveolar epithelial cell senescence.

Conclusions:

  • m6A alterations are prevalent in IPF, with METTL14 downregulation playing a potential role in disease progression.
  • METTL14's effect on DDIT4 mRNA stability suggests a novel epigenetic mechanism in IPF pathogenesis.
  • METTL14 represents a potential therapeutic target for epigenetic intervention in IPF.
Keywords:
DDIT4Idiopathic pulmonary fibrosisMETTL14agingm6A

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