Resistance to cisplatin (CDDP) remains a major challenge for the treatment of gastric cancer (GC). Circular RNAs (circRNAs) have been implicated in the development of CDDP resistance of GC. However, the precise actions of circ_0001017 in CDDP resistance of GC remain to be elucidated. The levels of circ_0001017, microRNA (miR)-543 and PH-domain and leucine-rich repeat protein phosphatase 2 (PHLPP2) mRNA were gauged by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was used to analyze the protein levels of Vimentin, N-cadherin, E-cadherin, and PHLPP2. Ribonuclease R (RNase R) assay was applied to evaluate the stability of circ_0001017. Cell viability and proliferation, colony formation ability, cell cycle distribution and apoptosis, and migration and invasion were detected by the Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and transwell assays, respectively. Direct relationship between miR-543 and circ_0001017 or PHLPP2 was verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft model assay was used to assess the function of circ_0001017 in vivo. Low expression of circ_0001017 was associated with CDDP resistance of GC. Enforced expression of circ_0001017 impeded growth, metastasis, and enhanced apoptosis of HGC-27/R and AGS/R cells and sensitized them to CDDP in vitro. Circ_0001017 targeted miR-543, and circ_0001017 regulated CDDP-resistant cell behaviors and CDDP sensitivity by suppressing miR-543. PHLPP2 was a direct target of miR-543, and circ_0001017 controlled PHLPP2 expression through miR-543. Moreover, miR-543 knockdown-mediated promotion of PHLPP2 impacted CDDP-resistant cell behaviors and CDDP sensitivity in vitro. Additionally, elevated expression of circ_0001017 hindered growth of HGC-27/R cells and sensitized them to CDDP in vivo. Our findings demonstrated that enforced expression of circ_0001017 suppressed malignant behaviors and enhanced CDDP sensitivity of CDDP-resistant GC cells at least partially by the miR-543/PHLPP2 axis.

顺铂耐药（CDDP）仍然是胃癌（GC）治疗的主要挑战。环状 RNA (circRNA) 与 GC 的 CDDP 抗性发展有关。然而，circ_0001017 在 GC 的 CDDP 抗性中的确切作用仍有待阐明。通过定量实时聚合酶链反应 (qRT-PCR) 测量 circ_0001017、microRNA (miR)-543 和 PH 结构域和富含亮氨酸的重复蛋白磷酸酶 2 (PHLPP2) mRNA 的水平。Western印迹用于分析波形蛋白、N-钙粘蛋白、E-钙粘蛋白和PHLPP2的蛋白质水平。应用核糖核酸酶 R (RNase R) 测定法评估 circ_0001017 的稳定性。Cell Counting Kit-8 (CCK-8) 检测细胞活力和增殖、集落形成能力、细胞周期分布和凋亡、迁移和侵袭，菌落形成、流式细胞术和 transwell 检测。miR-543 与 circ_0001017 或 PHLPP2 之间的直接关系通过双荧光素酶报告基因和 RNA 免疫沉淀 (RIP) 测定得到验证。异种移植模型试验用于评估 circ_0001017 在体内的功能。circ_0001017 的低表达与 GC 的 CDDP 抗性有关。circ_0001017 的强制表达阻碍了 HGC-27/R 和 AGS/R 细胞的生长、转移和增强的凋亡，并使它们在体外对 CDDP 敏感。circ_0001017 靶向 miR-543，circ_0001017 通过抑制 miR-543 调节 CDDP 抗性细胞行为和 CDDP 敏感性。PHLPP2 是 miR-543 的直接靶标，circ_0001017 通过 miR-543 控制 PHLPP2 的表达。而且，miR-543 敲低介导的 PHLPP2 促进在体外影响 CDDP 抗性细胞行为和 CDDP 敏感性。此外，circ_0001017 的表达升高阻碍了 HGC-27/R 细胞的生长，并使它们在体内对 CDDP 敏感。我们的研究结果表明，circ_0001017 的强制表达至少部分通过 miR-543/PHLPP2 轴抑制了恶性行为并增强了 CDDP 抗性 GC 细胞的 CDDP 敏感性。