Journal
INTERNATIONAL JOURNAL OF ONCOLOGY
Volume 50, Issue 3, Pages 942-952Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2017.3849
Keywords
LSD1; cyclin D1; endometrial cancer; PI3K/AKT; PTEN; estrogen
Categories
Funding
- National Key Clinical Specialist Construction Programs of China
- National Natural Science Foundation of China [81201541, 81502230, 81402134]
- Shanghai Pu Jiang Talent Program [12PJDO02]
Ask authors/readers for more resources
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 (beta-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 Dl. Interfering with cyclin Dl leads to PI3K/AKT signal suppression. Re-overexpression of cyclin Dl 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available