Department of General Surgery, Taizhou First People's Hospital, Taizhou, 318020, China.
Emergency Department, Taizhou First People's Hospital, Taizhou, 318020, China.
Appl Biochem Biotechnol. 2023 Mar;195(3):1644-1655. doi: 10.1007/s12010-022-04219-6. Epub 2022 Nov 10.
Cisplatin broadly functions as a routine treatment for lung adenocarcinoma (LUAD) patients. However, primary and acquired cisplatin resistances frequently occur in the treatment of LUAD patients, seriously affecting the therapeutic effect of cisplatin in patients. We intended to illustrate the impact of let-7c-5p/cell division cycle 25A (CDC25A) axis on cisplatin resistance in LUAD. Expression of let-7c-5p and CDC25A was analyzed via quantitative real-time polymerase chain reaction. The interaction between the two was verified by dual-luciferase reporter detection. For detecting half-maximal inhibitory concentration value of cisplatin in LUAD cells and cell proliferation, we separately applied Cell Counting Kit-8 and colony formation assays. Furthermore, we measured cell apoptosis and cell cycle distribution via flow cytometry, as well as cell cycle-related protein expression via Western blot. Let-7c-5p was evidently downregulated in LUAD, while CDC25A was remarkably upregulated. Let-7c-5p upregulation arrested LUAD cells to proliferate, stimulated cell apoptosis, and arrested cell cycle in G0/G1 phase, thus enhancing sensitivity of LUAD cells to cisplatin. In terms of mechanism, CDC25A was directly targeted by let-7c-5p, and the influence of let-7c-5p overexpression on LUAD proliferation, apoptosis, cell cycle, and cisplatin resistance could be reversed by CDC25A upregulation. Let-7c-5p improved sensitivity of LUAD cells to cisplatin by modulating CDC25A, and let-7c-5p/CDC25A axis was an underlying target for the intervention of LUAD cisplatin resistance.
顺铂广泛用作肺腺癌 (LUAD) 患者的常规治疗方法。然而，在 LUAD 患者的治疗中，经常会出现原发性和获得性顺铂耐药，严重影响顺铂在患者中的治疗效果。我们旨在阐明 let-7c-5p/细胞分裂周期 25A (CDC25A) 轴对 LUAD 顺铂耐药的影响。通过定量实时聚合酶链反应分析 let-7c-5p 和 CDC25A 的表达。通过双荧光素酶报告基因检测验证两者之间的相互作用。为了检测 LUAD 细胞中顺铂的半数最大抑制浓度值和细胞增殖，我们分别应用细胞计数试剂盒-8 和集落形成测定法。此外，我们通过流式细胞术测量细胞凋亡和细胞周期分布，以及通过 Western blot 测量细胞周期相关蛋白的表达。let-7c-5p 在 LUAD 中明显下调，而 CDC25A 明显上调。let-7c-5p 的上调使 LUAD 细胞停止增殖，刺激细胞凋亡，并将细胞周期阻滞在 G0/G1 期，从而增强 LUAD 细胞对顺铂的敏感性。就机制而言，CDC25A 是 let-7c-5p 的直接靶标，let-7c-5p 过表达对 LUAD 增殖、凋亡、细胞周期和顺铂耐药的影响可以通过 CDC25A 的上调来逆转。let-7c-5p 通过调节 CDC25A 提高 LUAD 细胞对顺铂的敏感性，let-7c-5p/CDC25A 轴是 LUAD 顺铂耐药干预的潜在靶点。
