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CircPLK1 upregulates ETS1 to confer anthracycline resistance in triple-negative breast cancer

Danian Dai1, Jinhui Zhang2, Yunxian Mo2

  • 1Department of Plastic and Peripheral Vascular Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China.

Journal of Translational Internal Medicine
|September 2, 2025
PubMed
Abstract

Insights

Circular RNA circPLK1 promotes triple-negative breast cancer (TNBC) resistance to anthracycline chemotherapy. Inhibiting circPLK1 may offer a new therapeutic strategy for TNBC patients with poor prognosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) are implicated in triple-negative breast cancer (TNBC) development.
  • The role of circRNAs in TNBC chemotherapy resistance is not well understood.
  • This study investigates circPLK1's function in anthracycline resistance in TNBC.

Purpose of the Study:

  • To determine the biological effect of circPLK1 on anthracycline resistance in TNBC.
  • To explore the mechanism by which circPLK1 influences chemotherapy resistance.
  • To assess the prognostic value of circPLK1 in TNBC patients.

Main Methods:

  • circRNA microarray identified circPLK1 in TNBC cells and samples.
  • Functional assays included cytotoxicity, colony formation, and flow cytometry.
  • Expression analysis used qRT-PCR, Western blot, in situ hybridization, and immunohistochemistry.
  • Interaction studies involved RNA immunoprecipitation and luciferase reporter assays.

Main Results:

  • Upregulated circPLK1 in non-complete pathological response (pCR) TNBC patients correlated with aggressive traits.
  • Overexpression of circPLK1 enhanced TNBC cell resistance to doxorubicin, while knockdown inhibited it.
  • circPLK1 promoted doxorubicin resistance in a TNBC xenograft model.
  • circPLK1 acts as a sponge for miR-940, upregulating ETS1 expression.
  • High circPLK1 and ETS1 expression are linked to reduced TNBC patient survival.

Conclusions:

  • circPLK1 significantly contributes to anthracycline resistance in TNBC.
  • circPLK1 is associated with a poor prognosis in TNBC patients.
  • Targeting circPLK1 could be a viable therapeutic strategy to overcome anthracycline resistance in TNBC.
Keywords:
ETS1PLK1anthracycline resistancecircular RNAtriple-negative breast cancer

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