Open Access

p53 performs an essential role in mediating the oncogenic stimulus triggered by loss of expression of neurofibromatosis type 2 during in vitro tumor progression

  • Authors:
    • Xiye Li
    • Hongsai Chen
    • Lu Xue
    • Xiuhong Pang
    • Xiaoman Zhang
    • Zhengjie Zhu
    • Weidong Zhu
    • Zhaoyan Wang
    • Hao Wu
  • View Affiliations

  • Published online on: June 21, 2017     https://doi.org/10.3892/ol.2017.6445
  • Pages: 2223-2231
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The loss of the tumor suppressor neurofibromatosis type 2 gene, encoding merlin, has been considered to be a fundamental event during the malignant progression of various cell types. However, a consensus for the mainstream mechanism, by which merlin deficiency contributes to uncontrolled cellular proliferation, has not been reached. The present study aimed to determine whether silencing of merlin using lentivirus‑based short hairpin RNA potentiates cellular proliferation and cell cycle progression in human colon carcinoma HCT116 cell lines, expressing p53. The present results demonstrated that merlin knockdown contributed to cellular proliferation and G1/S cell cycle progression to a greater extent in HCT116 cells wide‑type for p53 (p53wt) compared with p53‑null (p53‑/‑) cells. This was supported by overexpression experiments which demonstrated a significant inhibitory effect of excess merlin on cellular proliferation only in HCT116 p53wt cells. In order to investigate the underlying mechanisms of action, the expression of p53‑involved G1/S transition genes was evaluated by western blot analysis. For HCT116 p53wt cells, merlin loss suppressed p53 expression, and therefore the dysregulation of cell cycle regulatory proteins, including p21, cyclin D1/cyclin‑dependent kinase (CDK)4 and cyclin E1/CDK2 complexes. However, merlin knockdowns had no impact on the expression of any of the aforementioned molecules in p53‑/‑ cells, indicating that lack of merlin resulted in G1/S cell cycle progression, and thereby uncontrolled cellular proliferation mainly via the regulation of p53‑mediated pathways. Taken together, it was proposed that p53 performs an essential role in mediating the oncogenic stimulus triggered by merlin loss, and p53 is a molecule that should be investigated for its potential in targeted drug therapy for merlin‑deficient malignancies.
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August-2017
Volume 14 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Copy and paste a formatted citation
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Spandidos Publications style
Li X, Chen H, Xue L, Pang X, Zhang X, Zhu Z, Zhu W, Wang Z and Wu H: p53 performs an essential role in mediating the oncogenic stimulus triggered by loss of expression of neurofibromatosis type 2 during in vitro tumor progression. Oncol Lett 14: 2223-2231, 2017.
APA
Li, X., Chen, H., Xue, L., Pang, X., Zhang, X., Zhu, Z. ... Wu, H. (2017). p53 performs an essential role in mediating the oncogenic stimulus triggered by loss of expression of neurofibromatosis type 2 during in vitro tumor progression. Oncology Letters, 14, 2223-2231. https://doi.org/10.3892/ol.2017.6445
MLA
Li, X., Chen, H., Xue, L., Pang, X., Zhang, X., Zhu, Z., Zhu, W., Wang, Z., Wu, H."p53 performs an essential role in mediating the oncogenic stimulus triggered by loss of expression of neurofibromatosis type 2 during in vitro tumor progression". Oncology Letters 14.2 (2017): 2223-2231.
Chicago
Li, X., Chen, H., Xue, L., Pang, X., Zhang, X., Zhu, Z., Zhu, W., Wang, Z., Wu, H."p53 performs an essential role in mediating the oncogenic stimulus triggered by loss of expression of neurofibromatosis type 2 during in vitro tumor progression". Oncology Letters 14, no. 2 (2017): 2223-2231. https://doi.org/10.3892/ol.2017.6445