Open Access

NEK2 promotes hepatocellular carcinoma migration and invasion through modulation of the epithelial-mesenchymal transition

  • Authors:
    • Yi Zhang
    • Wei Wang
    • Yifei Wang
    • Xiaohui Huang
    • Zhaohui Zhang
    • Bin Chen
    • Wenxuan Xie
    • Shaoqiang Li
    • Shunli Shen
    • Baogang Peng
  • View Affiliations

  • Published online on: January 22, 2018     https://doi.org/10.3892/or.2018.6224
  • Pages: 1023-1033
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Never in mitosis gene-A (NIMA)-related expressed kinase 2 (NEK2) has been recently reported to play a role in tumor progression, drug resistance and tumorigenesis. However, little is known about the effects of NEK2 in hepatocellular carcinoma (HCC) metastasis and the underlying mechanism. NEK2 expression levels were examined by immunochemistry, qRT‑PCR and western blot analyses in HCC cell lines and HCC tissues. A Transwell assay was used to determine the migration and invasion capacity of NEK2-silenced or NEK2-overexpressing HCC cells. Cell proliferation was investigated by MTT [(3-(4,5)-dimethylthiazol(-z-y1)-3,5-di-phenytetrazolium bromide] assay. The expression levels of epithelial-mesenchymal transition (EMT) markers in NEK2-silenced or NEK2-overexpressing HCC cells were examined by western blot analyses and qRT‑PCR. The correlations between NEK2 expression and clinicopathological characteristics were further analyzed. Gene microarray was further used to analyze the effect of NEK2 expression on downstream cell signals. Our study showed that NEK2 was overexpressed in human HCC (37.84%; 98/259). NEK2 overexpression was significantly associated with liver non‑capsulation and predicted poor survival outcomes in HCC patients after hepatectomy. In addition, NEK2 significantly enhanced HCC cell invasive ability. Mechanistically, we found that the epithelial-mesenchymal transition (EMT) plays a pivotal role in the NEK2-mediated promotion of HCC cell invasion. Furthermore, we provided evidence that signaling through the Wnt, NF-κB, focal adhesion, VEGF, Hippo and p53 pathways may be downstream of NEK2. Our findings highlight the importance of NEK2 in HCC metastasis and suggest that NEK2 is a reliable prognostic marker for HCC patients after hepatectomy.
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March-2018
Volume 39 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Zhang Y, Wang W, Wang Y, Huang X, Zhang Z, Chen B, Xie W, Li S, Shen S, Peng B, Peng B, et al: NEK2 promotes hepatocellular carcinoma migration and invasion through modulation of the epithelial-mesenchymal transition. Oncol Rep 39: 1023-1033, 2018
APA
Zhang, Y., Wang, W., Wang, Y., Huang, X., Zhang, Z., Chen, B. ... Peng, B. (2018). NEK2 promotes hepatocellular carcinoma migration and invasion through modulation of the epithelial-mesenchymal transition. Oncology Reports, 39, 1023-1033. https://doi.org/10.3892/or.2018.6224
MLA
Zhang, Y., Wang, W., Wang, Y., Huang, X., Zhang, Z., Chen, B., Xie, W., Li, S., Shen, S., Peng, B."NEK2 promotes hepatocellular carcinoma migration and invasion through modulation of the epithelial-mesenchymal transition". Oncology Reports 39.3 (2018): 1023-1033.
Chicago
Zhang, Y., Wang, W., Wang, Y., Huang, X., Zhang, Z., Chen, B., Xie, W., Li, S., Shen, S., Peng, B."NEK2 promotes hepatocellular carcinoma migration and invasion through modulation of the epithelial-mesenchymal transition". Oncology Reports 39, no. 3 (2018): 1023-1033. https://doi.org/10.3892/or.2018.6224