Proliferation and invasion of colon cancer cells are suppressed by knockdown of TOP2A

J Cell Biochem. 2018 Sep;119(9):7256-7263. doi: 10.1002/jcb.26916. Epub 2018 May 15.

Abstract

Recent research has shown that TOP2A plays an important role in the tumorigenesis of many malignancies, such as breast cancer, ovarian cancer, and prostate cancer. However, few studies have been conducted on TOP2A expression and functions in colon cancer. In the present study, we found that TOP2A expression was obviously elevated in colon cancer tissues compared to adjacent non-cancerous tissues. Depletion of TOP2A in HCT116 and SW480 colon cancer cells by transfection of specific small interfering RNA significantly suppressed proliferation and inhibited invasion of cells, even induced apoptosis as indicated by both MTT assay, Annexin V/propidium iodide staining, and Transwell assay. Furthermore, we explored the underlying mechanisms. Knockdown of TOP2A not only affects the expression of cell apoptosis-related (Bcl-2 and Bax) and invasion-related proteins (MMP-2 and MMP-9), but also reduced the phosphorylation levels of ERK and AKT. In conclusion, we showed that TOP2A was upregulated in colon cancer tissue samples and that TOP2A may serve as an oncogene in colon cancer.

Keywords: TOP2A; colon cancer cells; invasion; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Apoptosis
  • Cell Proliferation*
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / metabolism*
  • DNA Topoisomerases, Type II / genetics*
  • DNA Topoisomerases, Type II / metabolism*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • HCT116 Cells
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Neoplasm Invasiveness*
  • Neoplasm Staging
  • Poly-ADP-Ribose Binding Proteins / genetics*
  • Poly-ADP-Ribose Binding Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Small Interfering / genetics
  • Transfection
  • Up-Regulation
  • bcl-2-Associated X Protein / metabolism

Substances

  • BAX protein, human
  • BCL2 protein, human
  • Poly-ADP-Ribose Binding Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Small Interfering
  • bcl-2-Associated X Protein
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • DNA Topoisomerases, Type II
  • TOP2A protein, human