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Hsa_circ_0079530/AQP4 轴与非小细胞肺癌的发生发展及放射敏感性相关。

Hsa_circ_0079530/AQP4 Axis Is Related to Non-Small Cell Lung Cancer Development and Radiosensitivity.

机构信息

Department of Oncology, Changsha Central Hospital, Changsha, China.

Interventional Therapy Centre, Changsha Central Hospital, Changsha, China.

出版信息

Ann Thorac Cardiovasc Surg. 2022 Oct 20;28(5):307-319. doi: 10.5761/atcs.oa.21-00237. Epub 2022 Jul 26.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

Circ_0079530 silence repressed cell proliferation, migration, and invasion, and facilitated radiosensitivity in NSCLC cells by mediating miR-409-3p/AQP4 axis.

摘要

背景

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。

方法

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。

结果

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。

结论

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3818/9585336/332fb30d9098/atcs-28-307-g001.jpg

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