Overexpression of lysine-specific demethylase 1 in ovarian endometriomas and its inhibition reduces cellular proliferation, cell cycle progression, and invasiveness

摘要

Objective To investigate whether lysine-specific demethylase 1 (LSD1) is aberrantly expressed in endometriomas and whether treatment with tranylcypromine, an LSD1 inhibitor, has any effect on cell viability, cell cycle, and invasiveness. Design Laboratory study using human tissues. Setting Academic hospital. Patient(s) Forty-two ectopic endometrial tissue samples, their homologue eutopic endometrial tissue samples, and 70 control endometrial tissue samples. Intervention(s) Immunohistochemistry analysis of LSD1 of all human tissue samples, and Western blot analysis, quantitative real-time reverse-transcription polymerase chain reaction analysis, cell viability assay, cell cycle analysis, and invasion assay of eutopic and ectopic endometriotic stromal cells and normal endometrial stromal cells. Main Outcome Measure(s) Immunostaining levels of LSD1, gene and protein expression levels, cell viability, cell cycles, and invasiveness. Result(s) The expression of the LSD1 gene and protein in endometriosis was elevated. Treatment of endometriotic stromal cells with tranylcypromine statistically significantly reduced the cellular proliferation, cell cycle progression, and invasiveness. Conclusion(s) Because DNA and histones are intimately intertwined and work in concert in transcription regulation, conceivably histone demethylation activity of LSD1 could be wide ranging. The inhibition of LSD1 activity by tranylcypromine and the resultant inhibition of proliferation, cell cycle progression, and invasiveness suggest that LSD1 may be a candidate therapeutic target for endometriosis.