Forkhead-box A1 induces cell senescence in endometrial cancer by regulating p16INK4a

  • Authors:
    • Jingyun Wang
    • Yiding Bian
    • Yun Liao
    • Ye Xia
    • Xiaoping Wan
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  • Published online on: June 23, 2016     https://doi.org/10.3892/or.2016.4907
  • Pages: 795-802
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Abstract

We previously identified FOXA1 as a tumor-suppressor in EC cells. In the present study, we sought to delineate the different roles of FOXA1 associated with cell senescence and further investigated the correlation between FOXA1 and p16INK4a in the progression of EC. Using reverse transcription-quantitative PCR (RT-qPCR), we found that FOXA1 expression was significantly downregulated in EC cells compared to that in normal endometrial cells. Functionally, senescence‑associated β-galactosidase staining, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), clonogenic and Transwell assays showed that in addition to acting as a pioneer factor, FOXA1 was significantly upregulated in senescent EC cells. Furthermore, restoration of FOXA1 expression triggered multiple steps of cellular senescence in EC cells and activated p16INK4a expression. All of these findings indicate that FOXA1 promotes cell senescence in EC by interaction with p16INK4a, possibly via the AKT pathway. Notably, a selective PI3K inhibitor raised the possibility that FOXA1‑induced senescence is associated with the AKT pathway in EC cells. Collectively, the present study provides a conceivable molecular mechanism by which cell senescence acts as the barrier to EC, and is regulated by FOXA1-induced p16INK4a expression. This may be a newly identified regulatory mechanism of cell senescence in EC.
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August-2016
Volume 36 Issue 2

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

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Spandidos Publications style
Wang J, Bian Y, Liao Y, Xia Y and Wan X: Forkhead-box A1 induces cell senescence in endometrial cancer by regulating p16INK4a. Oncol Rep 36: 795-802, 2016.
APA
Wang, J., Bian, Y., Liao, Y., Xia, Y., & Wan, X. (2016). Forkhead-box A1 induces cell senescence in endometrial cancer by regulating p16INK4a. Oncology Reports, 36, 795-802. https://doi.org/10.3892/or.2016.4907
MLA
Wang, J., Bian, Y., Liao, Y., Xia, Y., Wan, X."Forkhead-box A1 induces cell senescence in endometrial cancer by regulating p16INK4a". Oncology Reports 36.2 (2016): 795-802.
Chicago
Wang, J., Bian, Y., Liao, Y., Xia, Y., Wan, X."Forkhead-box A1 induces cell senescence in endometrial cancer by regulating p16INK4a". Oncology Reports 36, no. 2 (2016): 795-802. https://doi.org/10.3892/or.2016.4907