tRF-Leu reverse breast cancer cells chemoresistance by regulation of BIRC5

  • Discov Oncol. 2024 Sep 15;15(1):449. doi: 10.1007/s12672-024-01317-1.
Li Sun  #  1  2 ,  Yu-Wen Jiao  #  2 ,  Fu-Qi Cui  3 ,  Jin Liu  3 ,  Zhong-Ya Xu  4 ,  Dong-Lin Sun  5
Affiliations
  • 1. Hepatopancreatobiliary Surgery Department, The Third Affiliated Hospital of Soochow University, Changzhou First People's Hospital, Changzhou, China.
  • 2. Department of General Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China.
  • 3. Department Graduate School of Dalian Medical University, Dalian Medical University, Dalian, China.
  • 4. Children's Hospital of Nanjing Medical University, Nanjing, China. [email protected].
  • 5. Hepatopancreatobiliary Surgery Department, The Third Affiliated Hospital of Soochow University, Changzhou First People's Hospital, Changzhou, China. [email protected].
  • # Contributed equally.
PMID: 39278863 DOI: 10.1007/s12672-024-01317-1
Abstract

Objective: Accumulating studies reported the crucial roles of tRFs in tumorigenesis. However, their further mechanisms and clinical values remains unclear. This study aimed at the further investigation of tRF-Leu in breast Cancer chemotherapy resistance.

Methods: The high-throughput Sequencing was performed and identified the downregulation of tRF-Leu in MCF7/ADR cells. The function of tRF-Leu in breast Cancer cells and breast Cancer chemotherapy resistance was investigated in vitro and in vivo, including colony formation assay, CCK-8 assay, transwell assay and Apoptosis assay. The binding site of tRF-Leu on BIRC5 was verified by dual-luciferase assay.

Results: tRF-Leu was downregulated in MCF7/ADR cells. Overexpression of tRF-Leu inhibited the migration of breast Cancer cells. Furthermore, tRF-Leu could reverse the resistance of MCF7/ADR cells to Adriamycin both in vitro and in vivo. BIRC5 was a target of tRF-Leu, which might be involved in the chemotherapy resistance regulation.

Conclusion: We demonstrated that tRF-Leu could inhibit the chemotherapy resistance of breast Cancer by targeting BIRC5. These findings might identify new biomarkers of breast Cancer therapy and bring new strategies to reverse chemotherapy resistance.

Keywords
BIRC5; Breast cancer; Chemotherapy resistance; TRF.
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