Department of Thoracic Surgery, West China Hospital, Sichuan University , Chengdu, Sichuan, China.
Department of Thoracic Surgery, Huaihe Hospital of Henan University , Kaifeng, Henan, China.
Cell Cycle. 2021 Jan;20(2):166-178. doi: 10.1080/15384101.2020.1867780. Epub 2021 Jan 8.
Circular RNAs (circRNAs) have been reported to be related to the development of human cancers. However, the function of circ-FOXM1 in non-small cell lung cancer (NSCLC) was largely unknown. Here, we revealed the role and functional mechanism of circ-FOXM1 in NSCLC progression. The relative expression of circ-FOXM1, microRNA-149-5p (miR-149-5p), and autophagy-related 5 (ATG5) was determined by quantitative real-time polymerase chain reaction (RT-qPCR). Cell Counting Kit-8 (CCK-8), flow cytometry, and transwell assay were employed to assess cell viability, apoptosis, and migration, respectively. The relative protein expression was detected by western blot. Furthermore, mouse xenograft was carried out to analyze the effect of circ-FOXM1 on tumor growth . In addition, the interaction between miR-149-5p and circ-FOXM1 or ATG5 was predicted by Starbase3.0 and confirmed by the dual-luciferase reporter assay and RNA pull-down assay. Circ-FOXM1 and ATG5 levels were upregulated, while the miR-149-5p level was downregulated in NSCLC tissues and cells. Circ-FOXM1 knockdown suppressed NSCLC cell viability, migration, and autophagy, and induced cell apoptosis. Interestingly, circ-FOXM1 targeted miR-149-5p to upregulate the ATG5 level. Moreover, circ-FOXM1 exerted function through repressing miR-149-5p expression, and miR-149-5p exerted function via inhibiting ATG5 expression. Our results suggested that circ-FOXM1 knockdown attenuated the development of NSCLC through modulating the miR-149-5p/ATG5 axis, providing a theoretical basis for the therapy of NSCLC.
环形 RNA（circRNAs）已被报道与人类癌症的发生发展有关。然而，circ-FOXM1 在非小细胞肺癌（NSCLC）中的作用在很大程度上尚不清楚。在这里，我们揭示了 circ-FOXM1 在 NSCLC 进展中的作用和功能机制。通过实时定量聚合酶链反应（RT-qPCR）测定 circ-FOXM1、微小 RNA-149-5p（miR-149-5p）和自噬相关 5（ATG5）的相对表达量。细胞计数试剂盒-8（CCK-8）、流式细胞术和 Transwell 测定分别用于评估细胞活力、凋亡和迁移。通过 Western blot 检测相对蛋白表达。此外，进行了小鼠异种移植以分析 circ-FOXM1 对肿瘤生长的影响。此外，通过 Starbase3.0 预测 miR-149-5p 与 circ-FOXM1 或 ATG5 之间的相互作用，并通过双荧光素酶报告基因检测和 RNA 下拉实验进行验证。在 NSCLC 组织和细胞中，circ-FOXM1 和 ATG5 水平上调，而 miR-149-5p 水平下调。circ-FOXM1 敲低抑制 NSCLC 细胞活力、迁移和自噬，并诱导细胞凋亡。有趣的是，circ-FOXM1 通过靶向 miR-149-5p 来上调 ATG5 水平。此外，circ-FOXM1 通过抑制 miR-149-5p 的表达发挥作用，而 miR-149-5p 通过抑制 ATG5 的表达发挥作用。我们的结果表明，circ-FOXM1 敲低通过调节 miR-149-5p/ATG5 轴来减弱 NSCLC 的发展，为 NSCLC 的治疗提供了理论依据。
