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Article Open Access

Emodin inhibits TGF-β2 by activating the FOXD3/miR‑199a axis in ovarian cancer cells in vitro

  • Authors:
    • Kejuan Song
    • Teng Lv
    • Yulong Chen
    • Yuchao Diao
    • Qin Yao
    • Yankui Wang
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
    Copyright: © Song et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2063-2070
    |
    Published online on: March 6, 2018
       https://doi.org/10.3892/or.2018.6301
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Abstract

Ovarian cancer is a highly metastatic malignancy and a leading cause of cancer-related death in postmenopausal women. Emodin is a natural anthraquinone isolated from several traditional Chinese medicines including Rhubarb and Polygonum cuspidatum. Recently, emodin was demonstrated to reduce the growth of human ovarian carcinoma cells. However, the mechanism remains unclear. In the present study, we identified that transforming growth factor (TGF)-β2 was significantly affected by emodin treatment in A2780 cells using microarray analysis. MicroRNA (miR)-199a was predicted as a potential miRNA targeting TGF-β2 by in silico prediction using TargetScan. The mRNA and protein levels of TGF-β2 were both significantly reduced by miR-199a. Spearman's correlation analysis revealed a significant correlation between the expression level of miR-199a and TGF-β2 in human ovarian cancer specimens. Silencing of miR-199a with miR-199a inhibitor significantly restored the reduction in TGF-β2 expression induced by emodin. Additionally, cell viability and colony formation of A2780 cells were markedly inhibited by emodin treatment, which was mediated by miR-199a. We analyzed the primary mature miR-199a-1 and miR-199a-2 transcripts in A2780 cells treated with emodin or dimethyl sulfoxide (DMSO) and found that only pri-miR-199a-1 was regulated by emodin. A conserved binding site of Forkhead box D3 (FOXD3) was identified within pri-miR‑199a-1. We further revealed that miR-199a expression was significantly regulated by FOXD3. Taken together, the present study demonstrated that emodin may directly promote FOXD3 expression and sequentially activates miR-199a, which in turn suppresses the expression of TGF-β2 to reduce cell viability and colony formation of A2780 cells.
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Copy and paste a formatted citation
Spandidos Publications style
Song K, Lv T, Chen Y, Diao Y, Yao Q and Wang Y: Emodin inhibits TGF-β2 by activating the FOXD3/miR‑199a axis in ovarian cancer cells in vitro. Oncol Rep 39: 2063-2070, 2018.
APA
Song, K., Lv, T., Chen, Y., Diao, Y., Yao, Q., & Wang, Y. (2018). Emodin inhibits TGF-β2 by activating the FOXD3/miR‑199a axis in ovarian cancer cells in vitro. Oncology Reports, 39, 2063-2070. https://doi.org/10.3892/or.2018.6301
MLA
Song, K., Lv, T., Chen, Y., Diao, Y., Yao, Q., Wang, Y."Emodin inhibits TGF-β2 by activating the FOXD3/miR‑199a axis in ovarian cancer cells in vitro". Oncology Reports 39.5 (2018): 2063-2070.
Chicago
Song, K., Lv, T., Chen, Y., Diao, Y., Yao, Q., Wang, Y."Emodin inhibits TGF-β2 by activating the FOXD3/miR‑199a axis in ovarian cancer cells in vitro". Oncology Reports 39, no. 5 (2018): 2063-2070. https://doi.org/10.3892/or.2018.6301
Copy and paste a formatted citation
x
Spandidos Publications style
Song K, Lv T, Chen Y, Diao Y, Yao Q and Wang Y: Emodin inhibits TGF-β2 by activating the FOXD3/miR‑199a axis in ovarian cancer cells in vitro. Oncol Rep 39: 2063-2070, 2018.
APA
Song, K., Lv, T., Chen, Y., Diao, Y., Yao, Q., & Wang, Y. (2018). Emodin inhibits TGF-β2 by activating the FOXD3/miR‑199a axis in ovarian cancer cells in vitro. Oncology Reports, 39, 2063-2070. https://doi.org/10.3892/or.2018.6301
MLA
Song, K., Lv, T., Chen, Y., Diao, Y., Yao, Q., Wang, Y."Emodin inhibits TGF-β2 by activating the FOXD3/miR‑199a axis in ovarian cancer cells in vitro". Oncology Reports 39.5 (2018): 2063-2070.
Chicago
Song, K., Lv, T., Chen, Y., Diao, Y., Yao, Q., Wang, Y."Emodin inhibits TGF-β2 by activating the FOXD3/miR‑199a axis in ovarian cancer cells in vitro". Oncology Reports 39, no. 5 (2018): 2063-2070. https://doi.org/10.3892/or.2018.6301
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