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METTL3 promotes tumour development by decreasing APC expression mediated by APC mRNA N -methyladenosine-dependent YTHDF binding

Nature Communications, ISSN: 2041-1723, Vol: 12, Issue: 1, Page: 3803
2021
  • 108
    Citations
  • 0
    Usage
  • 35
    Captures
  • 1
    Mentions
  • 1
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    108
  • Captures
    35
  • Mentions
    1
    • News Mentions
      1
      • News
        1
  • Social Media
    1
    • Shares, Likes & Comments
      1
      • Facebook
        1

Most Recent News

METTL3 promotes glycolysis and cholangiocarcinoma progression by mediating the m6A modification of AKR1B10

Abstract Objective N6-methyladenosine (m6A) RNA methylation is involved in governing the mechanism of tumor progression. We aimed to excavate the biological role and mechanism of

Article Description

The adenomatous polyposis coli (APC) is a frequently mutated tumour suppressor gene in cancers. However, whether APC is regulated at the epitranscriptomic level remains elusive. In this study, we analysed TCGA data and separated 200 paired oesophageal squamous cell carcinoma (ESCC) specimens and their adjacent normal tissues and demonstrated that methyltransferase-like 3 (METTL3) is highly expressed in tumour tissues. mA-RNA immunoprecipitation sequencing revealed that METTL3 upregulates the mA modification of APC, which recruits YTHDF for APC mRNA degradation. Reduced APC expression increases the expression of β-catenin and β-catenin-mediated cyclin D1, c-Myc, and PKM2 expression, thereby leading to enhanced aerobic glycolysis, ESCC cell proliferation, and tumour formation in mice. In addition, downregulated APC expression correlates with upregulated METTL3 expression in human ESCC specimens and poor prognosis in ESCC patients. Our findings reveal a mechanism by which the Wnt/β-catenin pathway is upregulated in ESCC via METTL3/YTHDF-coupled epitranscriptomal downregulation of APC.

Bibliographic Details

Wang, Wei; Shao, Fei; Yang, Xueying; Wang, Juhong; Zhu, Rongxuan; Yang, Yannan; Zhao, Gaoxiang; Guo, Dong; Sun, Yingli; Wang, Jie; Xue, Qi; Gao, Shugeng; Gao, Yibo; He, Jie; Lu, Zhimin

Springer Science and Business Media LLC

Chemistry; Biochemistry, Genetics and Molecular Biology; Physics and Astronomy

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