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Abstract：
DNA topoisomerase II alpha (TOP2A) expression, gene alterations, and enzyme activity have been studied in various malignant tumors. Abnormal elevation of TOP2A expression is considered to be related to the development of non-small cell lung cancer (NSCLC). However, its association with tumor metastasis and its mode of action remains unclear. Bioinformatics, real-time quantitative PCR, immunohistochemistry and immunoblotting were used to detect TOP2A expression in NSCLC tissues and cells. Cell migration and invasion assays as well as cytoskeletal staining were performed to analyze the effects of TOP2A on the motility, migration and invasion ability of NSCLC cells. Cell cycle and apoptosis assays were used to verify the effects of TOP2A on apoptosis as well as cycle distribution in NSCLC. TOP2A expression was considerably upregulated in NSCLC and significantly correlated with tumor metastasis and the occurrence of epithelial-mesenchymal transition (EMT) in NSCLC. Additionally, by interacting with the classical ligand Wnt3a, TOP2A may trigger the canonical Wnt signaling pathway in NSCLC. These observations suggest that TOP2A promotes EMT in NSCLC by activating the Wnt/β-catenin signaling pathway and positively regulates malignant events in NSCLC, in addition to its significant association with tumor metastasis. TOP2A promotes the metastasis of NSCLC by stimulating the canonical Wnt signaling pathway and inducing EMT. This study further elucidates the mechanism of action of TOP2A, suggesting that it might be a potential therapeutic target for anti-metastatic therapy.
摘要：
DNA拓扑异构酶Ⅱα（TOP2A）表达，基因改变，和酶活性已经在各种恶性肿瘤中进行了研究。TOP2A表达异常升高被认为与非小细胞肺癌(NSCLC)的发生发展有关。然而,其与肿瘤转移的关系及其作用方式尚不清楚。生物信息学,实时定量PCR,免疫组化和免疫印迹法检测TOP2A在NSCLC组织和细胞中的表达。进行细胞迁移和侵袭测定以及细胞骨架染色以分析TOP2A对运动性的影响，NSCLC细胞的迁移和侵袭能力。细胞周期和凋亡测定用于验证TOP2A对NSCLC细胞凋亡以及周期分布的影响。TOP2A在NSCLC中表达明显上调，与NSCLC中肿瘤转移和上皮间质转化（EMT）的发生密切相关。此外,通过与经典配体Wnt3a相互作用，TOP2A可能在NSCLC中触发经典的Wnt信号通路。这些观察结果表明，TOP2A通过激活Wnt/β-catenin信号通路促进NSCLC中的EMT，并积极调节NSCLC中的恶性事件。除了与肿瘤转移显著相关外。TOP2A通过刺激经典Wnt信号通路和诱导EMT促进NSCLC转移。本研究进一步阐明了TOP2A的作用机制,这表明它可能是一个潜在的抗转移治疗靶点。
