LSD1 sustains estrogen-driven endometrial carcinoma cell proliferation through the PI3K/AKT pathway via di-demethylating H3K9 of cyclin D1

  • Authors:
    • Chunqin Chen
    • Yanan Wang
    • Shiyu Wang
    • Yuan Liu
    • Jiawen Zhang
    • Yuyao Xu
    • Zhenbo Zhang
    • Wei Bao
    • Sufang Wu
  • View Affiliations

  • Published online on: January 16, 2017     https://doi.org/10.3892/ijo.2017.3849
  • Pages: 942-952
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Abstract

A recent study reported that histone lysine specific demethylase 1 (LSD1, KDM1A) is overexpressed in endometrioid endometrial carcinoma (EEC) and associated with tumor progression as well as poor prognosis. However, the physiological function and mechanism of LSD1 in endometrial cancer (EC) remains largely unknown. In this study, we demonstrate that β-estradiol (E2) treatment increased LSD1 expression via the GPR30/PI3K/AKT pathway in endometrial cancer cells. Both siGPR30 and the PI3K inhibitor LY294002 block this effect. RNAi-mediated silencing of LSD1 abolished estrogen-driven endometrial cancer cell (ECC) proliferation, and induced G1 cell arrest and apoptosis. Mechanistically, we find that LSD1 silencing results in PI3K/AKT signal inactivation, but without the elevation of PTEN expression as expected. This is because the inhibition of LSD1 induces dimethylation of lysine 9 on histone H3 (H3K9m2) accumulation at the promoter region of cyclin D1. Interfering with cyclin D1 leads to PI3K/AKT signal suppression. Re-overexpression of cyclin D1 in LSD1-knockdown ECCs reverses the LSD1 inhibitory action. Our finding connects estrogen signaling with epigenetic regulation in EEC and provides novel experimental support for LSD1 as a potential target for endometrial cancer therapeutics.
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March-2017
Volume 50 Issue 3

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

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Spandidos Publications style
Chen C, Wang Y, Wang S, Liu Y, Zhang J, Xu Y, Zhang Z, Bao W and Wu S: LSD1 sustains estrogen-driven endometrial carcinoma cell proliferation through the PI3K/AKT pathway via di-demethylating H3K9 of cyclin D1. Int J Oncol 50: 942-952, 2017.
APA
Chen, C., Wang, Y., Wang, S., Liu, Y., Zhang, J., Xu, Y. ... Wu, S. (2017). LSD1 sustains estrogen-driven endometrial carcinoma cell proliferation through the PI3K/AKT pathway via di-demethylating H3K9 of cyclin D1. International Journal of Oncology, 50, 942-952. https://doi.org/10.3892/ijo.2017.3849
MLA
Chen, C., Wang, Y., Wang, S., Liu, Y., Zhang, J., Xu, Y., Zhang, Z., Bao, W., Wu, S."LSD1 sustains estrogen-driven endometrial carcinoma cell proliferation through the PI3K/AKT pathway via di-demethylating H3K9 of cyclin D1". International Journal of Oncology 50.3 (2017): 942-952.
Chicago
Chen, C., Wang, Y., Wang, S., Liu, Y., Zhang, J., Xu, Y., Zhang, Z., Bao, W., Wu, S."LSD1 sustains estrogen-driven endometrial carcinoma cell proliferation through the PI3K/AKT pathway via di-demethylating H3K9 of cyclin D1". International Journal of Oncology 50, no. 3 (2017): 942-952. https://doi.org/10.3892/ijo.2017.3849