Department of Hand Surgery, Yantaishan Hospital, Yantai, China.
Department of Traumatology and Orthopaedics II Ward, Weifang People's Hospital, Weifang, China.
Cancer Biother Radiopharm. 2023 Nov;38(9):585-595. doi: 10.1089/cbr.2020.4240. Epub 2020 Dec 22.
Osteosarcoma (OS) is a common, aggressive primary sarcoma of bone. Drug resistance is a huge obstacle to chemotherapy for cancer. This study aimed to investigate the role and mechanism of circ_0002060 in OS resistance to doxorubicin (DOX). The levels of circ_0002060, miR-198, and ATP-binding cassette subfamily B member 1 (ABCB1) in OS tissues and DOX-resistant OS cells were measured by quantitative real-time polymerase chain reaction or Western blot assay. Kaplan-Meier analysis was performed to determine the relationship between circ_0002060 expression in OS tissues and overall survival of OS patients. The half-inhibitory concentration (IC50) of DOX was calculated using the Cell Counting Kit-8 (CCK-8) assay. Proliferation and apoptosis of DOX-resistant OS cells were assessed by colony formation assay and flow cytometry. The levels of apoptosis-related proteins in DOX-resistant OS cells were measured by Western blot assay. Xenograft assay was utilized to analyze the effect of circ_0002060 on DOX resistance . The interactions among circ_0002060, miR-198, and ABCB1 in DOX-resistant OS cells were confirmed by dual-luciferase reporter assay, RNA immunoprecipitation assay, or RNA pull-down assay. circ_0002060 and ABCB1 were upregulated, while miR-198 was downregulated in OS tissues and DOX-resistant OS cells. circ_0002060 silencing reduced DOX resistance and . Moreover, circ_0002060 enhanced DOX resistance by sponging miR-198. Besides, miR-198 decreased DOX resistance by binding to ABCB1. In addition, circ_0002060 sponged miR-198 to upregulate ABCB1 expression. circ_0002060 promoted DOX resistance and OS progression by regulating the miR-198/ABCB1 axis, suggesting that circ_0002060 might be a promising biomarker for OS therapy.
骨肉瘤（OS）是一种常见的侵袭性骨原发性肉瘤。耐药性是癌症化疗的巨大障碍。本研究旨在探讨 circ_0002060 在 OS 对阿霉素（DOX）耐药中的作用和机制。通过定量实时聚合酶链反应或 Western blot 分析测定 OS 组织和 DOX 耐药 OS 细胞中 circ_0002060、miR-198 和三磷酸腺苷结合盒亚家族 B 成员 1（ABCB1）的水平。通过 Kaplan-Meier 分析确定 OS 组织中 circ_0002060 表达与 OS 患者总生存期的关系。使用细胞计数试剂盒-8（CCK-8）测定 DOX 的半抑制浓度（IC50）。通过集落形成试验和流式细胞术评估 DOX 耐药 OS 细胞的增殖和凋亡。通过 Western blot 分析测定 DOX 耐药 OS 细胞中凋亡相关蛋白的水平。利用异种移植试验分析 circ_0002060 对 DOX 耐药的影响。通过双荧光素酶报告基因试验、RNA 免疫沉淀试验或 RNA 下拉试验证实 circ_0002060、miR-198 和 ABCB1 在 DOX 耐药 OS 细胞中的相互作用。circ_0002060 和 ABCB1 在 OS 组织和 DOX 耐药 OS 细胞中上调，而 miR-198 下调。circ_0002060 沉默降低了 DOX 耐药性和。此外，circ_0002060 通过海绵吸附 miR-198 增强了 DOX 耐药性。此外，miR-198 通过结合 ABCB1 降低了 DOX 耐药性。此外，circ_0002060 通过海绵吸附 miR-198 上调 ABCB1 表达。circ_0002060 通过调节 miR-198/ABCB1 轴促进 DOX 耐药和 OS 进展，提示 circ_0002060 可能成为 OS 治疗的有前途的生物标志物。
