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Updated: Jun 13, 2025

Modeling Chemotherapy Resistant Leukemia In Vitro
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tRF-Leu reverse breast cancer cells chemoresistance by regulation of BIRC5

Li Sun1,2, Yu-Wen Jiao2, Fu-Qi Cui3

  • 1Hepatopancreatobiliary Surgery Department, The Third Affiliated Hospital of Soochow University, Changzhou First People's Hospital, Changzhou, China.

Discover Oncology
|September 15, 2024
PubMed
Abstract

Insights

Small RNA fragments called tRF-Leu are downregulated in breast cancer cells, leading to chemotherapy resistance. Restoring tRF-Leu levels can reverse this resistance by targeting BIRC5, offering new therapeutic strategies for breast cancer.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Tumorigenesis involves small non-coding RNAs, including tRNA-derived fragments (tRFs).
  • The specific roles and clinical significance of tRFs in cancer, particularly breast cancer chemotherapy resistance, require further elucidation.

Purpose of the Study:

  • To investigate the function and mechanism of tRF-Leu in breast cancer chemotherapy resistance.
  • To explore the potential of tRF-Leu as a therapeutic target for overcoming drug resistance in breast cancer.

Main Methods:

  • High-throughput sequencing to identify differential expression of tRF-Leu in Adriamycin-resistant MCF7 cells (MCF7/ADR).
  • In vitro and in vivo functional assays (colony formation, CCK-8, transwell, apoptosis) to assess the role of tRF-Leu in breast cancer cell behavior and drug resistance.
  • Dual-luciferase assay to confirm BIRC5 as a direct target of tRF-Leu.

Main Results:

  • tRF-Leu was significantly downregulated in MCF7/ADR cells compared to sensitive cells.
  • Overexpression of tRF-Leu suppressed breast cancer cell migration and reversed Adriamycin resistance in vitro and in vivo.
  • BIRC5 was identified as a direct target of tRF-Leu, suggesting its involvement in regulating chemotherapy resistance.

Conclusions:

  • tRF-Leu acts as a tumor suppressor by inhibiting chemotherapy resistance in breast cancer through targeting BIRC5.
  • These findings highlight tRF-Leu as a potential biomarker and therapeutic agent for enhancing breast cancer treatment efficacy.
Keywords:
BIRC5Breast cancerChemotherapy resistanceTRF

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