Department of Clinical Laboratory, Sichuan Science City Hospital, Mianyang, PR China.
Department of Pediatric, Sichuan Science City Hospital, Mianyang, PR China.
Histol Histopathol. 2023 Jun;38(6):681-693. doi: 10.14670/HH-18-545. Epub 2022 Nov 16.
Circ_0079530 has been confirmed to be a novel potential oncogene in non-small cell lung cancer (NSCLC). This study aims to explore the role and mechanism of circ_0079530 in NSCLC progression.
Levels of circ_0079530, microRNA (miR)-584-5p, thrombospondin-2 (THBS2), PCNA, Bax, E-cadherin, and ki67 were detected by quantitative real-time PCR (qRT-PCR), western blotting and immunohistochemistry. The proliferation of NSCLC cells was measured using cell counting kit 8 (CCK8) assay, colony formation assay, and EdU staining. Cell apoptosis and motility were respectively detected by flow cytometry and transwell assays. Interaction between miR-584-5p and circ_0079530 or THBS2 was predicted by bioinformatics analysis and confirmed via luciferase reporter assay and RNA immunoprecipitation (RIP) assay. A xenograft tumor model was used to analyze the role of circ_0079530 in tumor growth in vivo.
Circ_0079530 was highly expressed in NSCLC tissues and cell lines. Circ_0079530 overexpression facilitated proliferation, migration, and invasion whereas it restrained the apoptosis of NSCLC cells. Circ_0079530 silence showed the opposite effects on the above malignant biological behaviors. Mechanistic analysis showed that circ_0079530 functioned as a sponge of miR-584-5p to relieve the suppressive action of miR-584-5p on its target THBS2. Additionally, circ_0079530 knockdown impeded the growth of xenografts in vivo.
Circ_0079530 promoted NSCLC progression by regulating the miR-584-5p/THBS2 axis, providing a possible circRNA-targeted therapy for NSCLC.
Circ_0079530 已被证实是非小细胞肺癌（NSCLC）中的一种新型潜在癌基因。本研究旨在探讨 Circ_0079530 在 NSCLC 进展中的作用和机制。
采用实时定量 PCR（qRT-PCR）、Western blot 和免疫组化检测 Circ_0079530、微小 RNA（miR）-584-5p、血小板反应蛋白-2（THBS2）、增殖细胞核抗原（PCNA）、Bax、E-钙黏蛋白和 ki67 的水平。采用细胞计数试剂盒 8（CCK8）测定、集落形成实验和 EdU 染色测定 NSCLC 细胞的增殖。通过流式细胞术和 Transwell 测定分别检测细胞凋亡和运动。通过生物信息学分析预测 miR-584-5p 与 Circ_0079530 或 THBS2 的相互作用，并通过荧光素酶报告基因测定和 RNA 免疫沉淀（RIP）测定进行验证。建立异种移植瘤模型，分析 Circ_0079530 在体内肿瘤生长中的作用。
Circ_0079530 在 NSCLC 组织和细胞系中高表达。Circ_0079530 过表达促进 NSCLC 细胞的增殖、迁移和侵袭，而抑制细胞凋亡。Circ_0079530 沉默则对上述恶性生物学行为产生相反的影响。机制分析表明，Circ_0079530 作为 miR-584-5p 的海绵，减轻了 miR-584-5p 对其靶标 THBS2 的抑制作用。此外，Circ_0079530 敲低抑制了体内异种移植瘤的生长。
Circ_0079530 通过调节 miR-584-5p/THBS2 轴促进 NSCLC 进展，为 NSCLC 的环状 RNA 靶向治疗提供了可能。
