CircRNA (circ)_0007823 Contributes to Triple-Negative Breast Cancer Progression and Cisplatin Resistance via the miR-182-5p/FOXO1 Pathway.

Abstract

Cisplatin (DDP) is used for the clinical management of triple-negative breast cancer (TNBC). However, the development of drug resistance limits its therapeutic efficacy. Circular RNAs (circRNAs) are known to be involved in tumor DDP resistance. In our previous study, we reported that circ_0007823 expression is downregulated and correlated with adverse prognosis in TNBC. However, its association with DDP resistance remains unclear. This study aimed to determine the role of circ_0007823 and miR-182-5p in DDP-resistant TNBC and explore the underlying mechanisms. First, expression profiles circ_0007823, microRNA (miR)-182-5p, and forkhead box O1 (FOXO1) in TNBC cells were determined. Additionally, biological characteristics of cells, including apoptosis, cell cycle, proliferation, and migration, were analyzed using various assays. Luciferase reporter and rescue assays were used to determine the correlations among circ_0007823, miR-182-5p, and FOXO1 expression. MiR-182-5p was overexpressed in DDP-resistant TNBC cells. MiR-182-5p knockdown suppressed the invasiveness and increased the apoptosis of drug-resistant cells, contributing to G1 arrest and S phase reduction. Mechanistically, circ_0007823 targeted miR-182-5p, and its overexpression drastically reduced the promotional effects of the miR-182-5p mimic on the aggression and transfer ability of drug-resistant cells. Furthermore, FOXO1 overexpression increased the sensitivity of cells to DDP and reduced their malignant progression. Therefore, FOXO1 was established as the downstream target of miR-182-5p that may be used to treat DDP-resistant TNBC. In summary, circ_0007823 overexpression attenuated DDP resistance in TNBC via the miR-182-5p-FOXO1 axis, indicating the therapeutic potential of circ_0007823 DDP-resistant TNBC treatment.