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.

顺铂（DDP）用于三阴性乳腺癌（TNBC）的临床治疗。然而，耐药性的发展限制了其治疗效果。已知环状 RNA (circRNA) 参与肿瘤 DDP 耐药性。在我们之前的研究中，我们报道了 circ_0007823 表达下调并与 TNBC 不良预后相关。然而，其与 DDP 耐药性的关系仍不清楚。本研究旨在确定circ_0007823和miR-182-5p在DDP耐药TNBC中的作用并探讨其潜在机制。首先，确定了 TNBC 细胞中 circ_0007823、microRNA (miR)-182-5p 和 forkhead box O1 (FOXO1) 的表达谱。此外，还使用各种分析方法分析了细胞的生物学特征，包括细胞凋亡、细胞周期、增殖和迁移。使用荧光素酶报告基因和救援测定来确定 circ_0007823、miR-182-5p 和 FOXO1 表达之间的相关性。 MiR-182-5p 在 DDP 抗性 TNBC 细胞中过表达。 MiR-182-5p 敲低可抑制耐药细胞的侵袭性并增加其凋亡，从而导致 G1 期停滞和 S 期减少。从机制上讲，circ_0007823靶向miR-182-5p，其过度表达大大降低了miR-182-5p模拟物对耐药细胞侵袭和转移能力的促进作用。此外，FOXO1 过表达增加了细胞对 DDP 的敏感性，并减少了细胞的恶性进展。因此，FOXO1被确定为miR-182-5p的下游靶点，可用于治疗DDP耐药的TNBC。总之，circ_0007823 过表达通过 miR-182-5p-FOXO1 轴减弱了 TNBC 中的 DDP 耐药性，表明 circ_0007823 DDP 耐药性 TNBC 治疗的治疗潜力。