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

BACKGROUND AND OBJECTIVES

Circular RNAs play a vital role in developing triple-negative breast cancer (TNBC). Likewise, the function of circRNAs in TNBC resistance to chemotherapy remains largely unknown. Here, we aimed to investigate whether circPLK1 has a biological efect on anthracycline resistance in TNBC.

METHODS

We identified circPLK1-a circRNA-using a circRNA microarray in TNBC cells and paired TNBC samples. We assessed the role of circPLK1 in anthracycline resistance in TNBC. Cytotoxicity assay, colony formation assay, and flow cytometry were performed as functional experiments. Western blot analysis, qRT-PCR, hybridization, and immunohistochemistry were used to evaluate the expression of circPLK1, miR-940, and ETS1. RNA immunoprecipitation and luciferase reporter assay were conducted to evaluate the interaction among circPLK1, miR-940, and ETS1. We evaluated the prognosis value of circPLK1 and ETS1 in 240 TNBC patients.

RESULTS

The upregulation of circPLK1 in non-pCR TNBC patients receiving anthracyclines-based neoadjuvant chemotherapy was significantly associated with aggressive characteristics. Colony formation and doxorubicin resistance of TNBC cells were promoted by circPLK1 overexpression but inhibited by circPLK1 knockdown . circPLK1 overexpression facilitated doxorubicin resistance of TNBC in the nude mouse xenograft model. We found that circPLK1 could promote ETS1 expression by sponging miR-940. High circPLK1 and ETS1 expression were significantly associated with reduced survival in TNBC.

CONCLUSION

circPLK1 plays a vital role in the resistance of TNBC to anthracycline and is associated with poor prognosis. The inhibition of circPLK1 may be a practical therapeutic approach to modulate anthracycline resistance in TNBC.