Department of Respiratory Medicine, Xiantao First People's Hospital Affiliated to Yangtze University, Xiantao City, Hubei Province, China.
Bioengineered. 2022 Mar;13(3):5126-5140. doi: 10.1080/21655979.2022.2036910.
Cisplatin (DDP) therapy is widely used for the treatment of non-small cell lung cancer (NSCLC), but the curative effect is limited by chemoresistance. This study was designed to explore circ_0020123 function in DDP resistance of NSCLCDDP. Expression detection for circ_0020123, microRNA-140-3p (miR-140-3p) and homeobox B5 (HOXB5) was performed by real-time polymerase chain reaction (qRT-PCR). Half inhibitory concentration (IC50) of DDP and cell proliferation was detected by Cell Counting Kit-8 (CCK-8) assay. Colony formation ability was assessed using colony formation assay. Cell migration and invasion were evaluated via transwell assay. Cell apoptosis was examined by flow cytometry. Protein analysis was conducted by Western blot. Dual-luciferase reporter assay was used to affirm target interaction. Circ_0020123 expression was upregulated in DDP-resistant NSCLC cells. DDP resistance was reduced by downregulation of circ_0020123 in NSCLC cells. Circ_0020123 was identified as a miR-140-3p sponge. The effect of si-circ_0020123 on DDP resistance was partly associated with miR-140-3p upregulation. HOXB5 was a downstream target for miR-140-3p. Overexpression of HOXB5 mitigated miR-140-3p-induced inhibition of DDP resistance in NSCLC cells. Circ_0020123 upregulated the level of HOXB5 partly via sponging miR-140-3p. Also, circ_0020123 promoted tumor growth in NSCLC/DDP xenografts by regulating miR-140-3p and HOXB5 levels at least in part. These results revealed that circ_0020123 promoted DDP resistance in NSCLC cells partly by targeting miR-140-3p/HOXB5 axis, indicating that circ_0020123 might be used as a molecular target in DDP treatment for NSCLC.
顺铂(DDP)疗法广泛用于治疗非小细胞肺癌(NSCLC),但疗效受到化疗耐药性的限制。本研究旨在探讨 circ_0020123 在 NSCLC 顺铂耐药中的作用。通过实时聚合酶链反应(qRT-PCR)检测 circ_0020123、微小 RNA-140-3p(miR-140-3p)和同源盒 B5(HOXB5)的表达。用细胞计数试剂盒-8(CCK-8)检测 DDP 的半抑制浓度(IC50)和细胞增殖。通过集落形成实验评估集落形成能力。通过 Transwell 测定评估细胞迁移和侵袭。通过流式细胞术检测细胞凋亡。通过 Western blot 进行蛋白分析。双荧光素酶报告实验用于确认靶标相互作用。在 DDP 耐药的 NSCLC 细胞中上调 circ_0020123 表达。下调 NSCLC 细胞中的 circ_0020123 可降低 DDP 耐药性。circ_0020123 被鉴定为 miR-140-3p 的海绵体。si-circ_0020123 对 DDP 耐药的影响部分与 miR-140-3p 上调有关。HOXB5 是 miR-140-3p 的下游靶标。过表达 HOXB5 可减轻 miR-140-3p 诱导的 NSCLC 细胞中 DDP 耐药性的抑制。circ_0020123 通过海绵 miR-140-3p 部分上调 HOXB5 的水平。此外,circ_0020123 通过调节 miR-140-3p 和 HOXB5 水平,至少部分地促进 NSCLC/DDP 异种移植物中的肿瘤生长。这些结果表明,circ_0020123 通过靶向 miR-140-3p/HOXB5 轴促进 NSCLC 细胞中的 DDP 耐药性,表明 circ_0020123 可能作为 NSCLC 中 DDP 治疗的分子靶标。