Kou Fan, Sun Houfang, Wu Lei, Li Baihui, Zhang Bailu, Wang Xuezhou, Yang Lili
Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
National Clinical Research Center for Cancer, Tianjin, China.
J Cancer. 2020 Feb 10;11(9):2496-2508. doi: 10.7150/jca.41415. eCollection 2020.
: Topoisomerase IIA (TOP2A) gene encodes DNA topoisomerase enzyme and has been reported that TOP2A is broadly expressed in many types of cancers. Our study aims to investigate the prognostic effect of TOP2A on lung adenocarcinoma (LUAD) and the potential molecular mechanism of TOP2A to tumorigenesis. : Bioinformatical analysis, real-time PCR and Western blot were applied to explore the expression level of TOP2A. Kaplan-Meier survival analysis was used to evaluate the effect of TOP2A on patients' prognosis. Cell proliferation, migration and invasion ability were examined by colony-formation, Cell Counting Kit-8 (CCK8) assay, wound healing assay and transwell invasion assay, respectively. : We firstly investigated differentially expressed genes in lung adenocarcinoma and normal tissues of GEO (tumor = 666, normal = 184) and TCGA (tumor = 517, normal = 59) and these data showed that TOP2A is broadly expressed in LUAD and the expression level of TOP2A is associated with poor prognosis, which indicated that TOP2A is an upregulated prognostic related gene in LUAD. Then we identified that the expression level of TOP2A was upregulated in both surgically removed lung cancer tissues and lung cancer cell lines. Knockdown of TOP2A in A549 and GLC82 cells inhibited cell proliferation, migration and invasion. Inhibition of TOP2A reduced the expression levels of CCNB1 and CCNB2, which indicated that TOP2A targeting CCNB1 and CCNB2 promotes GLC82 and A549 cells proliferation and metastasis. : Our study revealed an important role of TOP2A in LUAD, and may provide a potential prognostic indicator and target for cancer therapy.
拓扑异构酶IIA（TOP2A）基因编码DNA拓扑异构酶，据报道TOP2A在多种癌症中广泛表达。我们的研究旨在探讨TOP2A对肺腺癌（LUAD）的预后影响以及TOP2A在肿瘤发生中的潜在分子机制。：应用生物信息学分析、实时荧光定量PCR和蛋白质免疫印迹法来探究TOP2A的表达水平。采用Kaplan-Meier生存分析来评估TOP2A对患者预后的影响。分别通过集落形成实验、细胞计数试剂盒-8（CCK8）检测、伤口愈合实验和Transwell侵袭实验来检测细胞增殖、迁移和侵袭能力。：我们首先研究了基因表达综合数据库（GEO，肿瘤=666，正常=184）和癌症基因组图谱（TCGA，肿瘤=517，正常=59）中肺腺癌组织与正常组织中的差异表达基因，这些数据表明TOP2A在LUAD中广泛表达，且TOP2A的表达水平与预后不良相关，这表明TOP2A是LUAD中一个上调的预后相关基因。然后我们发现，在手术切除的肺癌组织和肺癌细胞系中TOP2A的表达水平均上调。在A549和GLC82细胞中敲低TOP2A可抑制细胞增殖、迁移和侵袭。抑制TOP2A可降低细胞周期蛋白B1（CCNB1）和细胞周期蛋白B2（CCNB2）的表达水平，这表明靶向CCNB1和CCNB2的TOP2A促进了GLC82和A549细胞的增殖和转移。：我们的研究揭示了TOP2A在LUAD中的重要作用，并可能为癌症治疗提供一个潜在的预后指标和靶点。
