Related Experiment Video

Updated: Jul 28, 2025

Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs
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Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs

Published on: May 10, 2018

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TROP2 translation mediated by dual m

Cong Chen1, Yinghui Chao2, Chengcheng Zhang1

  • 1Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.

Cancer Letters
|June 2, 2023
PubMed

Insights

Dual RNA modifications, messenger RNA N6-adenosine methylation (m6A) and transfer RNA 7-methylguanosine (m7G), promote bladder cancer (BCa) by enhancing oncogene TROP2 translation. Targeting METTL3 and METTL1 inhibits BCa progression.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cancer Research

Background:

  • RNA modifications like m6A and m7G are vital for RNA function.
  • The synergistic role of dual m6A/m7G modifications in bladder cancer (BCa) gene translation is not well understood.

Purpose of the Study:

  • To elucidate the mechanism of dual m6A/m7G RNA modifications in promoting TROP2 translation and BCa development.
  • To investigate the therapeutic potential of targeting these RNA epigenetic pathways.

Main Methods:

  • Investigated METTL3-mediated m6A modification of TROP2 mRNA and METTL1-mediated m7G modification of tRNA.
  • Assessed the impact of TROP2 inhibition and METTL3/METTL1 knockout on BCa cell behavior in vitro and in vivo.
  • Analyzed the correlation between TROP2, METTL3, and METTL1 expression in BCa patients.

Main Results:

  • METTL3 promotes TROP2 mRNA translation via m6A modification, while METTL1 enhances it through tRNA m7G modification.
  • Inhibition of TROP2 or combined knockout of METTL3/METTL1 suppressed BCa cell proliferation, invasion, and migration.
  • TROP2 overexpression partially rescued the inhibitory effects of METTL3/METTL1 knockout, and TROP2 levels correlated positively with METTL3 and METTL1 in patients.

Conclusions:

  • METTL3 and METTL1-mediated dual m6A/m7G RNA modifications synergistically enhance TROP2 translation, driving BCa progression.
  • This study reveals a novel RNA epigenetic mechanism in bladder cancer, highlighting TROP2, METTL3, and METTL1 as potential therapeutic targets.
Keywords:
Bladder cancerRNA modificationTROP2m(6)Am(7)G

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