FOXD1 is targeted by miR-30a-5p and miR-200a-5p and suppresses the proliferation of human ovarian carcinoma cells by promoting p21 expression in a p53-independent manner

  • Authors:
    • Yu Wang
    • Chunping Qiu
    • Nan Lu
    • Zhaojian Liu
    • Chengjuan Jin
    • Chenggong Sun
    • Hualei Bu
    • Hongfeng Yu
    • Samina Dongol
    • Beihua Kong
  • View Affiliations

  • Published online on: April 4, 2018     https://doi.org/10.3892/ijo.2018.4359
  • Pages: 2130-2142
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Abstract

High-grade serous ovarian carcinoma (HGSOC) accounts for the highest number of deaths among patients with epithelial ovarian cancer. However, the molecular mechanisms underlying HGSOC tumorigenesis are currently unclear. In the present study, a lentiviral expression system was employed to manipulate forkhead box D1 (FOXD1) expression in ovarian cancer cells. Immunohistochemical staining was used to examine the expression of FOXD1 in tissue samples. Clonogenic and MTT assays were employed to evaluate cell proliferation, and flow cytometry was applied for cell cycle analysis. Dual-luciferase reporter and chromatin immunoprecipitation assays were used to determine the role of FOXD1 in regulating p21 expression. The results demonstrated that FOXD1 expression was downregulated in HGSOC, and high expression levels of FOXD1 were found to be a predictor of good prognosis. FOXD1 significantly inhibited the proliferation of human ovarian cancer cells and induced cell cycle arrest at G1 phase in vitro. In addition, exogenous FOXD1 expression inhibited ovarian cancer cell growth in vivo. Furthermore, microRNA (miR)-30a-5p and miR-200a-5p were observed to be upregulated in HGSOC, and function as direct negative regulators of FOXD1 by targeting its 3'-untranslated region. The present study also revealed that FOXD1 promotes p21 expression in a p53-independent manner. In conclusion, the results of the present study indicate a direct association between FOXD1 and p21 that may be mediated by miR-30a-5p and miR-200a-5p. The authors hypothesize that FOXD1 may serve as a biomarker or therapeutic target in HGSOC.
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June-2018
Volume 52 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Wang Y, Qiu C, Lu N, Liu Z, Jin C, Sun C, Bu H, Yu H, Dongol S, Kong B, Kong B, et al: FOXD1 is targeted by miR-30a-5p and miR-200a-5p and suppresses the proliferation of human ovarian carcinoma cells by promoting p21 expression in a p53-independent manner . Int J Oncol 52: 2130-2142, 2018
APA
Wang, Y., Qiu, C., Lu, N., Liu, Z., Jin, C., Sun, C. ... Kong, B. (2018). FOXD1 is targeted by miR-30a-5p and miR-200a-5p and suppresses the proliferation of human ovarian carcinoma cells by promoting p21 expression in a p53-independent manner . International Journal of Oncology, 52, 2130-2142. https://doi.org/10.3892/ijo.2018.4359
MLA
Wang, Y., Qiu, C., Lu, N., Liu, Z., Jin, C., Sun, C., Bu, H., Yu, H., Dongol, S., Kong, B."FOXD1 is targeted by miR-30a-5p and miR-200a-5p and suppresses the proliferation of human ovarian carcinoma cells by promoting p21 expression in a p53-independent manner ". International Journal of Oncology 52.6 (2018): 2130-2142.
Chicago
Wang, Y., Qiu, C., Lu, N., Liu, Z., Jin, C., Sun, C., Bu, H., Yu, H., Dongol, S., Kong, B."FOXD1 is targeted by miR-30a-5p and miR-200a-5p and suppresses the proliferation of human ovarian carcinoma cells by promoting p21 expression in a p53-independent manner ". International Journal of Oncology 52, no. 6 (2018): 2130-2142. https://doi.org/10.3892/ijo.2018.4359