J Cancer 2020; 11(9):2496-2508. doi:10.7150/jca.41415

Research Paper

TOP2A Promotes Lung Adenocarcinoma Cells' Malignant Progression and Predicts Poor Prognosis in Lung Adenocarcinoma

Fan Kou1,2,3,4,5,#, Houfang Sun1,2,3,4,5#, Lei Wu1,2,3,4,5, Baihui Li1,2,3,4,5, Bailu Zhang1,2,3,4,5, Xuezhou Wang1,2,3,4,5, Lili Yang1,2,3,4,5✉

1. Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
2. National Clinical Research Center for Cancer, Tianjin, China.
3. Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.
4. Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
5. Tianjin's Clinical Research Center for Cancer, Tianjin, China.
#: These authors contributed equally to this article

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Citation:
Kou F, Sun H, Wu L, Li B, Zhang B, Wang X, Yang L. TOP2A Promotes Lung Adenocarcinoma Cells' Malignant Progression and Predicts Poor Prognosis in Lung Adenocarcinoma. J Cancer 2020; 11(9):2496-2508. doi:10.7150/jca.41415. Available from http://www.jcancer.org/v11p2496.htm

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Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: Our study revealed an important role of TOP2A in LUAD, and may provide a potential prognostic indicator and target for cancer therapy.

Keywords: topoisomerase IIA, lung cancer, p53 pathway, tumorigenesis