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Updated: Jul 11, 2025

Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
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Pan-cancer tRNA-derived fragment CAT1 coordinates RBPMS to stabilize NOTCH2 mRNA to promote tumorigenesis

Mengqian Yu1, Jiani Yi2, Qiongzi Qiu3

  • 1Department of Respiratory Medicine, Sir Run Run Shaw Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China; Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, China.

Cell Reports
|November 9, 2023
PubMed

Insights

A novel cancer-associated tRF, CAT1, is upregulated in tumors and promotes lung cancer progression by stabilizing NOTCH2 mRNA. Elevated plasma CAT1 levels indicate potential as a biomarker for lung cancer detection.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • RNA Biology

Background:

  • Transfer RNA-derived fragments (tRFs) are small non-coding RNAs implicated in disease pathophysiology.
  • The specific role of tRFs in cancer progression is not fully understood.
  • Identifying novel regulatory mechanisms in cancer is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the role of tRFs in cancer progression, focusing on lung cancer.
  • To identify and characterize a specific tRF involved in tumor development and prognosis.
  • To elucidate the molecular mechanism by which this tRF influences cancer signaling pathways.

Main Methods:

  • Pan-cancer analysis to identify upregulated tRFs.
  • In vitro and in vivo experiments to assess the functional role of CAT1 in lung cancer.
  • RNA-binding protein immunoprecipitation (RIP) assays to identify interacting proteins.
  • Western blotting and qRT-PCR to measure protein and mRNA levels.
  • Analysis of patient plasma samples for biomarker potential.

Main Results:

  • A pan-cancer 3'-tRF, termed CAT1 (cancer associated tRF 1), was found to be ubiquitously upregulated in tumors and associated with poor prognosis in various cancers, including lung cancer.
  • Upregulated CAT1 binds to RBPMS, displacing NOTCH2 and inhibiting its mRNA decay via the CCR4-NOT complex.
  • Enhanced NOTCH2 expression by CAT1 promotes lung cancer cell proliferation and metastasis in vitro and in vivo.
  • Plasma CAT1 levels were significantly increased in lung cancer patients compared to controls.

Conclusions:

  • Cancer-specific upregulation of CAT1 is intrinsically linked to cancer progression.
  • A 3'-tRF (CAT1) regulates NOTCH signaling in cancer.
  • CAT1 shows significant potential as a diagnostic biomarker for lung cancer.
Keywords:
CAT1CP: CancerCP: Molecular biologyNOTCH2RBPMSbiomarkergene regulationmRNA stabilitypan-cancer analysissmall noncoding RNAtRNA-derived fragmenttumorigenesis

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