Open Access

DNA topoisomerase 1 and 2A function as oncogenes in liver cancer and may be direct targets of nitidine chloride

  • Authors:
    • Li-Min Liu
    • Dan-Dan Xiong
    • Peng Lin
    • Hong Yang
    • Yi-Wu Dang
    • Gang Chen
  • View Affiliations

  • Published online on: August 21, 2018     https://doi.org/10.3892/ijo.2018.4531
  • Pages: 1897-1912
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to determine the role of topoisomerase 1 (TOP1) and topoisomerase 2A (TOP2A) in liver cancer (LC), and to investigate the inhibitory effect of nitidine chloride (NC) on these two topoisomerases. Immunohistochemistry (IHC) staining and microarray or RNA sequencing data mining showed markedly higher expression of TOP1 and TOP2A at the protein and mRNA levels in LC tissues compared with that in control non-tumor tissues. The prognostic values of TOP1 and TOP2A expression were also estimated based on data from The Cancer Genome Atlas. The elevated expression levels of TOP1 and TOP2A were closely associated with poorer overall survival and disease-free survival rates. When patients with LC were divided into high- and low-risk groups according to their prognostic index, TOP1 and TOP2A were highly expressed in the high-risk group. Bioinformatics analyses conducted on the co-expressed genes of TOP1 and TOP2A revealed that the topoisomerases were involved in several key cancer-related pathways, including the ‘p53 pathway’, ‘pathway in cancer’ and ‘apoptosis signaling pathway’. Reverse transcription-quantitative polymerase chain reaction and IHC performed on triplicate tumor tissue samples from LC xenografts in control or NC-treated nude mice showed that NC treatment markedly reduced the protein and mRNA expression of TOP1 and TOP2A in LC tissues. Molecular docking studies further confirmed the direct binding of NC to TOP1 and TOP2A. In conclusion, the present findings indicate that TOP1 and TOP2A are oncogenes in LC and could serve as potential biomarkers for the prediction of the prognosis of patients with LC and for identification of high-risk cases, thereby optimizing individual treatment management. More importantly, the findings support TOP1 and TOP2A as potential drug targets of NC for the treatment of LC.
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November-2018
Volume 53 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Liu L, Xiong D, Lin P, Yang H, Dang Y and Chen G: DNA topoisomerase 1 and 2A function as oncogenes in liver cancer and may be direct targets of nitidine chloride. Int J Oncol 53: 1897-1912, 2018
APA
Liu, L., Xiong, D., Lin, P., Yang, H., Dang, Y., & Chen, G. (2018). DNA topoisomerase 1 and 2A function as oncogenes in liver cancer and may be direct targets of nitidine chloride. International Journal of Oncology, 53, 1897-1912. https://doi.org/10.3892/ijo.2018.4531
MLA
Liu, L., Xiong, D., Lin, P., Yang, H., Dang, Y., Chen, G."DNA topoisomerase 1 and 2A function as oncogenes in liver cancer and may be direct targets of nitidine chloride". International Journal of Oncology 53.5 (2018): 1897-1912.
Chicago
Liu, L., Xiong, D., Lin, P., Yang, H., Dang, Y., Chen, G."DNA topoisomerase 1 and 2A function as oncogenes in liver cancer and may be direct targets of nitidine chloride". International Journal of Oncology 53, no. 5 (2018): 1897-1912. https://doi.org/10.3892/ijo.2018.4531