USP10 promotes proliferation and migration and inhibits apoptosis of endometrial stromal cells in endometriosis through activating the Raf-1/MEK/ERK pathway.

Endometriosis has been initially described as endometrial-like tissue outside of the uterine cavity. Mitogen-activated protein kinase/ERK kinase (MEK)/extracellular-signal-regulated kinase (ERK) signaling pathway playing an important role in the regulation of cell proliferation, apoptosis and migration has been found to be activated in endometriosis. However, the regulation of MEK/ERK signaling pathway in endometriosis has not been fully understood. In this study, primary-cultured endometrial stromal cells were collected from patients with endometriosis and healthy controls, and the proliferation, apoptosis and migration of ectopic endometrial stromal cells transfected with ubiquitin-specific protease 10 (USP10)-siRNA or pLVX-Puro-USP10 with or without MEK inhibitor PD98059 or exogenous signaling stimulation such as epidermal growth factor (EGF) were measured by CCK-8, flow cytometry and Transwell, respectively. The gene and protein expressions were measured by Real-time PCR or western blot. USP10 overexpression promoted ectopic endometrial stromal cell migration and proliferation, suppressed cell apoptosis, and activated MEK/ERK signaling that is a critical downstream target of the serine/threonine protein kinase Raf-1, which was significantly blocked by PD98059. USP10 silencing demonstrated the inverse effects, and these effects induced by USP10 silencing were significantly blocked by EGF. USP10 overexpression promoted Raf-1 protein expression, but not the mRNA expression, through deubiquitination. In conclusion, these results suggest that USP10 promotes proliferation and migration and inhibits apoptosis of endometrial stromal cells in endometriosis through activating the Raf-1/MEK/ERK pathway.