环状RNA ZNF609敲低通过miR-623/FOXM1轴抑制非小细胞肺癌的发展
CircRNA ZNF609 Knockdown Represses the Development of Non-Small Cell Lung Cancer via miR-623/FOXM1 Axis.
作者信息
Wang Fanghan, Li Xiangfeng, Jia Xigao, Geng Luxin
机构信息
Department of Oncology, 4th People's Hospital of Zibo, Zibo, Shandong, 255000, People's Republic of China.
Department of Radiology, 4th People's Hospital of Zibo, Zibo, Shandong, 255000, People's Republic of China.
出版信息
Cancer Manag Res. 2021 Feb 4;13:1029-1039. doi: 10.2147/CMAR.S282162. eCollection 2021.
BACKGROUND
The dysregulated circular RNAs (circRNAs) are relevant to the development of non-small cell lung cancer (NSCLC). Nevertheless, the function and mechanism of circRNA zinc finger protein 609 (circZNF609) in NSCLC development remain uncertain.
METHODS
Sixty-two NSCLC patients were recruited. circZNF609, microRNA-623 (miR-623) and forkhead box M1 (FOXM1) abundances were measured via quantitative reverse transcription polymerase chain reaction or Western blot. Cell viability, apoptosis, migration and invasion were analyzed via cell counting kit-8 (CCK8), flow cytometry, caspase3 activity, transwell assay and Western blot. The interaction between miR-623 and circZNF609 or FOXM1 was analyzed via dual-luciferase reporter analysis, RNA immunoprecipitation and pull-down. The function of circZNF609 on cell growth in vivo was tested via xenograft model.
RESULTS
circZNF609 abundance was enhanced in NSCLC tissues and cells. High expression of circZNF609 indicated the lower overall survival. circZNF609 interference restrained cell viability, migration and invasion and increased apoptosis. miR-623 was targeted via circZNF609. FOXM1 was targeted via miR-623 and regulated via circZNF609. miR-623 knockdown or FOXM1 overexpression mitigated the role of circZNF609 silence in NSCLC development. circZNF609 knockdown decreased NSCLC xenograft tumor growth.
CONCLUSION
circZNF609 knockdown repressed NSCLC development via regulating miR-623 and FOXM1.
背景
失调的环状RNA（circRNAs）与非小细胞肺癌（NSCLC）的发生发展相关。然而，环状RNA锌指蛋白609（circZNF609）在NSCLC发生发展中的功能和机制仍不明确。
方法
招募62例NSCLC患者。通过定量逆转录聚合酶链反应或蛋白质免疫印迹法检测circZNF609、微小RNA-623（miR-623）和叉头框蛋白M1（FOXM1）的丰度。通过细胞计数试剂盒-8（CCK8）、流式细胞术分析、caspase3活性检测、Transwell实验和蛋白质免疫印迹法分析细胞活力凋亡、迁移和侵袭情况。通过双荧光素酶报告基因分析、RNA免疫沉淀和下拉实验分析miR-623与circZNF609或FOXM1之间的相互作用。通过异种移植模型检测circZNF609对体内细胞生长的作用。
结果
circZNF609丰度在NSCLC组织和细胞中升高。circZNF609高表达提示总生存期较低。circZNF609干扰抑制细胞活力、迁移和侵袭并增加凋亡。miR-623是circZNF609的靶标。FOXM1是miR-623的靶标并受circZNF609调控。miR-623敲低或FOXM1过表达减轻了circZNF609沉默在NSCLC发生发展中的作用。circZNF609敲低减少了NSCLC异种移植瘤的生长。
结论
circZNF609敲低通过调控miR-623和FOXM1抑制NSCLC的发生发展。
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