Department of Thoracic Surgery, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, No.43 Renmin Avenue, Haikou City, 570208, Hainan Province, People's Republic of China.
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Hainan Medical University, Haikou, People's Republic of China.
Biochem Genet. 2024 Jun;62(3):1539-1555. doi: 10.1007/s10528-023-10493-8. Epub 2023 Aug 30.
Non-small cell lung cancer (NSCLC) is one of the most common and fatal cancers in the world. Circular RNA (circRNA) can broadly participate in the initiation and progression of the NSCLC. However, the regulatory mechanisms of circRNA in NSCLC remain poorly understood. In present study, we aimed to explore the potential role of circ_0101675 in the progression of NSCLC. Quantitative real-time polymerase chain reaction was performed to examine the expression of circ_0101675, microRNA-607 (miR-607) and programmed cell death receptor ligand 1 (PDL1) in NSCLC tissues and cells. Cell count kit 8 assay, colony formation assay, wound healing assay, transwell assay, tube formation assay and flow cytometry were applied to examine NSCLC cell proliferation, migration, invasion, angiogenesis and apoptosis. NSCLC cells were co-cultured with peripheral blood mononuclear cells to assess immune response. The protein levels of PDL1 and proteins related to apoptosis were detected by western blotting. Dual-luciferase reporter assay and RNA immunoprecipitation assay were conducted to verify the direct target site between miR-607 and circ_0101675 or PDL1. The experiments in vivo were employed to explore the effects of circ_0101675 on tumor growth in NSCLC. Circ_0101675 and PDL1 were high-expressed, while miR-607 was low-expressed in NSCLC cells and cancer tissues. The suppression of circ_0101675 suppressed growth, migration, invasion, angiogenesis and immune escape in NSCLC cells. Mechanistically, we found that high level of circ_0101675 could upregulate PDL1 expression via sponging miR-607. Moreover, the down-regulation of circ_0101675 inhibited the growth of NSCLC tumors in vivo by enhancing miR-607 expression to decrease PDL1 expression. Taken together, our results suggested that circ_0101675 might promote the proliferation, migration, invasion, and immune evasion abilities of NSCLC through miR-607/PDL1 axis.
非小细胞肺癌（NSCLC）是世界上最常见和最致命的癌症之一。环状 RNA（circRNA）可以广泛参与 NSCLC 的发生和发展。然而，circRNA 在 NSCLC 中的调控机制仍知之甚少。在本研究中，我们旨在探讨 circ_0101675 在 NSCLC 进展中的潜在作用。通过实时定量聚合酶链反应检测 NSCLC 组织和细胞中 circ_0101675、microRNA-607（miR-607）和程序性细胞死亡受体配体 1（PDL1）的表达。细胞计数试剂盒 8 检测试剂盒、集落形成检测试剂盒、划痕愈合检测试剂盒、Transwell 检测试剂盒、管形成检测试剂盒和流式细胞术检测 NSCLC 细胞增殖、迁移、侵袭、血管生成和凋亡。将 NSCLC 细胞与外周血单核细胞共培养以评估免疫反应。Western blot 检测 PDL1 蛋白水平及凋亡相关蛋白水平。双荧光素酶报告基因检测和 RNA 免疫沉淀检测验证 miR-607 与 circ_0101675 或 PDL1 之间的直接靶位。体内实验研究 circ_0101675 对 NSCLC 肿瘤生长的影响。circ_0101675 和 PDL1 在 NSCLC 细胞和癌组织中高表达，而 miR-607 低表达。抑制 circ_0101675 可抑制 NSCLC 细胞的生长、迁移、侵袭、血管生成和免疫逃逸。机制上，我们发现高水平的 circ_0101675 通过海绵吸附 miR-607 而上调 PDL1 表达。此外，下调 circ_0101675 通过增强 miR-607 表达降低 PDL1 表达，从而抑制 NSCLC 肿瘤在体内的生长。综上所述，我们的研究结果表明，circ_0101675 通过 miR-607/PDL1 轴促进 NSCLC 的增殖、迁移、侵袭和免疫逃逸能力。
