Open Access

Silencing of PPM1D inhibits cell proliferation and invasion through the p38 MAPK and p53 signaling pathway in papillary thyroid carcinoma

  • Authors:
    • Zhong‑Wu Lu
    • Duo Wen
    • Wen‑Jun Wei
    • Li‑Tao Han
    • Jun Xiang
    • Yu‑Long Wang
    • Yu Wang
    • Tian Liao
    • Qing‑Hai Ji
  • View Affiliations

  • Published online on: January 9, 2020     https://doi.org/10.3892/or.2020.7458
  • Pages: 783-794
  • Copyright: © Lu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Endeavors towards identifying key molecular markers for early diagnosis and treatment are driving the clinical study of papillary thyroid carcinoma (PTC). Recent studies have indicated that protein phosphatase, Mg2+/Mn2+ dependent, 1D (PPM1D) exerts an oncogenic function by increasing cell proliferation, migration and invasion in various cancer types. In addition, PPM1D has a high frequency of genetic alterations and has been proposed as a tumor driver in thyroid cancer, making PPM1D an attractive potential oncotarget for cancer treatment. The aims of the present study were to investigate the downstream targets of PPM1D and the potential molecular mechanisms of its oncogenic activities, as well as its clinical significance in PTC. As anticipated, PPM1D overexpression was confirmed in PTC clinical specimens. Furthermore, knockdown of PPM1D in thyroid cancer cell lines significantly suppressed the proliferation, migration and invasion but facilitated cell apoptosis. The protein levels of phosphorylated p38 mitogen‑activated protein kinase (MAPK), p53 and Bax were increased in PPM1D‑knockdown cells, while inhibition of p38 phosphorylation restored cell migration, proliferation and cell apoptosis. In addition, silencing of PPM1D expression induced nuclear translocation of p53 in K‑1 and TPC‑1 cells. The present results demonstrated that PPM1D regulated p38 MAPK and p53 signaling pathways to promote thyroid cancer progression. Collectively with the clinical results, these data qualified PPM1D as a potential diagnostic biomarker and therapeutic target in human thyroid cancer.

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March 2020
Volume 43 Issue 3

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

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APA
Lu, Z., Wen, D., Wei, W., Han, L., Xiang, J., Wang, Y. ... Ji, Q. (2020). Silencing of PPM1D inhibits cell proliferation and invasion through the p38 MAPK and p53 signaling pathway in papillary thyroid carcinoma. Oncology Reports, 43, 783-794. https://doi.org/10.3892/or.2020.7458
MLA
Lu, Z., Wen, D., Wei, W., Han, L., Xiang, J., Wang, Y., Wang, Y., Liao, T., Ji, Q."Silencing of PPM1D inhibits cell proliferation and invasion through the p38 MAPK and p53 signaling pathway in papillary thyroid carcinoma". Oncology Reports 43.3 (2020): 783-794.
Chicago
Lu, Z., Wen, D., Wei, W., Han, L., Xiang, J., Wang, Y., Wang, Y., Liao, T., Ji, Q."Silencing of PPM1D inhibits cell proliferation and invasion through the p38 MAPK and p53 signaling pathway in papillary thyroid carcinoma". Oncology Reports 43, no. 3 (2020): 783-794. https://doi.org/10.3892/or.2020.7458