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

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.

Expression of the Topoisomerase II Alpha (TOP2A) Gene in Lung Adenocarcinoma Cells and the Association with Patient Outcomes

“…It has been reported that cell division stops when the protein expression of TOP2A is silenced in human cells [ 25 ]. Accordingly, TOP2A is a cell proliferation-related protein, whose expression promotes the completion of cell division [ 11 , 17 ]. TOP2A gene expression has been found to be related to cell mitosis in S phase in breast cancer [ 7 , 26 , 27 ], and there is significant expression of TOP2A in different subtypes of breast cancer.…”

“…Basic research revealed that the knockdown of TOP2A can retard cell proliferation and suppress tumor formation [ 25 ]. It has also been proposed that TOP2A is a core protease that promotes and maintains tumor progression in tumor cells [ 13 , 17 , 25 ]. In assessing the role of the TOP2A gene, most studies focused on breast cancer, gastric cancer, liver cancer, prostate cancer, colorectal cancer, and esophageal cancer [ 6 , 27 , 30 – 33 ].…”

“…In assessing the role of the TOP2A gene, most studies focused on breast cancer, gastric cancer, liver cancer, prostate cancer, colorectal cancer, and esophageal cancer [ 6 , 27 , 30 – 33 ]. Increasingly more studies have been reported focusing on the effect of TOP2A gene on the clinical development and prognosis of lung adenocarcinoma [ 13 , 14 ]. For example, Fan Kou et al demonstrated in their research that TOP2A could promote lung adenocarcinoma cells’ malignant progression and predict poor prognosis in lung adenocarcinoma [ 14 ].…”

“…Significantly, TOP2A is essentially involved in various cell biological processes, such as DNA replication, chromatin condensation, chromosome separation, and structural maintenance of chromosomes [ 8 , 10 – 12 ]. Accordingly, multiple studies have been published to support that TOP2A gene expression is strongly associated with the occurrence and development of many tumors [ 13 – 17 ]. There have been reports focusing on the role of TOP2A gene in the development of LUAD [ 13 , 14 ].…”

“…Accordingly, multiple studies have been published to support that TOP2A gene expression is strongly associated with the occurrence and development of many tumors [ 13 – 17 ]. There have been reports focusing on the role of TOP2A gene in the development of LUAD [ 13 , 14 ]. For instance, Ma et al proposed in their latest research that LUAD is the core gene in the LUAD-related gene network [ 13 ].…”