Department of Oncology, Changsha Central Hospital, Changsha, China.
Interventional Therapy Centre, Changsha Central Hospital, Changsha, China.
Ann Thorac Cardiovasc Surg. 2022 Oct 20;28(5):307-319. doi: 10.5761/atcs.oa.21-00237. Epub 2022 Jul 26.
Circular RNAs are associated with non-small cell lung cancer (NSCLC) development and radiosensitivity. Nevertheless, the function and regulation mechanism of hsa_circ_0079530 (circ_0079530) in NSCLC development and radiosensitivity are largely unknown.
The abundances of circ_0079530, microRNA (miR-409-3p), aquaporin 4 (AQP4), E-cadherin, intercellular adhesion molecule-1, vitronectin, proliferating cell nuclear antigen, and matrix metalloproteinase 9 were determined via quantitative reverse transcription polymerase chain reaction or western blotting. Cell proliferation, survival fraction, cycle process, migration, invasion, and in vivo growth were examined by cell counting kit-8, colony formation, flow cytometry, transwell, and xenograft analyses. The binding relationship was assessed via dual-luciferase reporter assay and RNA immunoprecipitation assay.
Circ_0079530 expression was increased in NSCLC tissues and radioresistant samples. Circ_0079530 knockdown restrained cell proliferation, migration, and invasion, and facilitated radiosensitivity. Circ_0079530 silence decreased tumor growth with or without radiation treatment. Circ_0079530 was verified as a miR-409-3p sponge, and miR-409-3p downregulation mitigated the effects of circ_0079530 interference on NSCLC cell malignancy and radiosensitivity. AQP4 was directly targeted by miR-409-3p. MiR-409-3p restrained cell proliferation, migration, and invasion, and enhanced radiosensitivity by decreasing AQP4 expression. Notably, circ_0079530 silence decreased AQP4 expression by regulating miR-409-3p expression.
Circ_0079530 silence repressed cell proliferation, migration, and invasion, and facilitated radiosensitivity in NSCLC cells by mediating miR-409-3p/AQP4 axis.
环状 RNA 与非小细胞肺癌(NSCLC)的发生和放射敏感性有关。然而,hsa_circ_0079530(circ_0079530)在 NSCLC 发生和放射敏感性中的功能和调控机制在很大程度上尚不清楚。
通过定量逆转录聚合酶链反应或 Western blot 测定 circ_0079530、微小 RNA(miR-409-3p)、水通道蛋白 4(AQP4)、上皮钙黏附蛋白、细胞间黏附分子 1、纤连蛋白、增殖细胞核抗原和基质金属蛋白酶 9 的丰度。通过细胞计数试剂盒-8、集落形成、流式细胞术、Transwell 和异种移植分析检测细胞增殖、存活分数、周期进程、迁移、侵袭和体内生长。通过双荧光素酶报告基因检测和 RNA 免疫沉淀分析评估结合关系。
circ_0079530 在 NSCLC 组织和耐放射样本中表达增加。circ_0079530 敲低抑制细胞增殖、迁移和侵袭,并促进放射敏感性。circ_0079530 沉默抑制肿瘤生长,无论是否进行放射治疗。circ_0079530 被证实为 miR-409-3p 的海绵,并且 miR-409-3p 的下调减轻了 circ_0079530 干扰对 NSCLC 细胞恶性程度和放射敏感性的影响。AQP4 是 miR-409-3p 的直接靶点。miR-409-3p 通过降低 AQP4 表达抑制细胞增殖、迁移和侵袭,并增强放射敏感性。值得注意的是,circ_0079530 沉默通过调节 miR-409-3p 表达降低了 AQP4 表达。
circ_0079530 沉默通过调节 miR-409-3p/AQP4 轴抑制 NSCLC 细胞增殖、迁移和侵袭,并增强放射敏感性。