Abstract
BackgroundChemotherapeutic resistance is the main cause of clinical treatment failure and poor prognosis in triple-negative breast cancer (TNBC). There is no research on chemotherapeutic resistance in TNBC from the perspective of circular RNAs (circRNAs).MethodsTNBC-related circRNAs were identified based on the GSE101124 dataset. Quantitative reverse transcription PCR was used to detect the expression level of circWAC in TNBC cells and tissues. Then, in vitro and in vivo functional experiments were performed to evaluate the effects of circWAC in TNBC.ResultsCircWAC was highly expressed in TNBC and was associated with worse TNBC patient prognosis. Subsequently, it was verified that downregulation of circWAC can increase the sensitivity of TNBC cells to paclitaxel (PTX) in vitro and in vivo. The expression of miR-142 was negatively correlated with circWAC in TNBC. The interaction between circWAC and miR-142 in TNBC cells was confirmed by RNA immunoprecipitation assays, luciferase reporter assays, pulldown assays, and fluorescence in situ hybridization. Mechanistically, circWAC acted as a miR-142 sponge to relieve the repressive effect of miR-142 on its target WWP1. In addition, the overall survival of TNBC patients with high expression of miR-142 was significantly better than that of patients with low expression of miR-142, and these results were verified in public databases. MiR-142 regulated the expression of WWP1 and the activity of the PI3K/AKT pathway. It was confirmed that WWP1 is highly expressed in TNBC and that the prognosis of patients with high WWP1 expression is poor.ConclusionsCircWAC/miR-142/WWP1 form a competing endogenous RNA (ceRNA) network to regulate PI3K/AKT signaling activity in TNBC cells and affect the chemosensitivity of cells.
Highlights
Chemotherapeutic resistance is the main cause of clinical treatment failure and poor prognosis in triple-negative breast cancer (TNBC)
Thirty samples of TNBC tumor tissues and adjacent tissues were randomly selected from the biological sample bank of the First Affiliated Hospital of Soochow University for Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis
The results showed that the expression of hsa_circ_0007503 in TNBC tumor tissues was significantly higher than that in adjacent tissues
Summary
Chemotherapeutic resistance is the main cause of clinical treatment failure and poor prognosis in triple-negative breast cancer (TNBC). In China, there were approximately 270,000 new cases of breast cancer and 70,000 deaths in 2015 [4]. TNBC tissues are negative for ER, PR and HER-2; their sensitivity to endocrine therapies, molecular targeted therapies and chemotherapeutics is reduced, increasing the difficulty of clinical treatment. Adjuvant chemotherapy, such as anthracycline and paclitaxel (PTX)-based chemotherapy regimens, is still the main treatment method, but the development of chemotherapeutic resistance is still the main cause of clinical treatment failure and poor prognosis in breast cancer patients, and the 5-year survival rate of TNBC is significantly lower than that of non-TNBC breast cancers [6]. It is extremely urgent to improve the efficacy of TNBC therapies and prolong the patient survival time
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