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METTL3/YTHDF2 m6 A axis promotes tumorigenesis by degrading SETD7 and KLF4 mRNAs in bladder cancer

Haiyun Xie1, Jiangfeng Li1, Yufan Ying1

  • 1Department of Urology, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.

Journal of Cellular and Molecular Medicine
|March 4, 2020
PubMed

Insights

N6-Methyladenosine (m6A) RNA modification promotes bladder cancer (BCa) by degrading tumor suppressor mRNAs. Targeting the METTL3/YTHDF2 axis could offer new therapeutic strategies for BCa treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • N6-Methyladenosine (m6A) is the most common mRNA modification in eukaryotes.
  • m6A modification plays a role in various cancers, but its specific function in bladder cancer (BCa) remains unclear.

Purpose of the Study:

  • To investigate the role and mechanism of the m6A axis in bladder cancer progression.
  • To identify potential therapeutic targets for BCa.

Main Methods:

  • Depletion of METTL3 in vitro and in vivo.
  • Transcriptome sequencing.
  • m6A methylated RNA immunoprecipitation (MeRIP) and RIP assays.
  • Overexpression of SETD7 and KLF4.

Main Results:

  • METTL3 depletion inhibited BCa proliferation and metastasis.
  • The METTL3/YTHDF2 m6A axis was found to directly degrade the mRNAs of tumor suppressors SETD7 and KLF4.
  • Restoring SETD7 and KLF4 levels mimicked the effects of depleting the m6A axis.

Conclusions:

  • The METTL3/YTHDF2/SETD7/KLF4 m6A axis promotes bladder cancer progression.
  • This axis represents a potential therapeutic target for BCa.
Keywords:
METTL3/YTHDF2 m6A axisRNA modificationbladder cancercarcinogenesismRNA degradation

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