tsRNA-10547 generated by m1A modification-mediated tRNA shearing promotes colorectal cancer metastasis via

Xujun Song1, Qinjie Liu1, Qingsong Tao1

  • 1Department of Gastrointestinal Surgery, Zhongda Hospital, Southeast University, Nanjing, 210009, China.

Insights

Transfer RNA-derived fragments (tsRNAs) promote colorectal cancer (CRC) growth and metastasis by degrading CHRNA9 mRNA. This TRMT10C-mediated process highlights tsRNAs as potential therapeutic targets for CRC metastasis.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Transfer RNA-derived fragments (tsRNAs) are emerging regulators in tumorigenesis.
  • The specific role of tsRNAs in colorectal cancer (CRC) metastasis is not well understood.

Purpose of the Study:

  • To investigate the function and mechanism of tsRNA-10547 in CRC growth and metastasis.
  • To explore the relationship between tsRNA-10547, TRMT10C, and CHRNA9 in CRC.

Main Methods:

  • In vitro and in vivo functional experiments.
  • Transcriptome sequencing, RNA pull-down, RIP assays, and site-directed mutagenesis.
  • Analysis of clinical samples and bioinformatics datasets (GSE140327).

Main Results:

  • tsRNA-10547 was significantly upregulated in CRC tumors.
  • Overexpression of tsRNA-10547 enhanced CRC cell proliferation, migration, invasion, and lung metastasis.
  • TRMT10C, a methyltransferase producing tsRNA-10547, was also upregulated and promoted metastasis via tsRNA-10547.
  • tsRNA-10547 directly targeted CHRNA9 mRNA, leading to its degradation and suppression.
  • tsRNA-10547 functions via the RISC complex, interacting with AGO2 to degrade CHRNA9 mRNA.

Conclusions:

  • TRMT10C-mediated m1A modification promotes tsRNA-10547 biogenesis.
  • tsRNA-10547 accelerates CRC growth and lung metastasis by degrading CHRNA9 mRNA.
  • This study reveals a novel mechanism of CRC metastasis and suggests tsRNAs as potential therapeutic targets.

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