Abstract
Endometriosis is a common gynecological disease characterized by diminished apoptosis, sustained ectopic survival of dysfunctional endometrial cells. Hypoxia has been implicated as a crucial microenvironmental factor that contributes to endometriosis. It has been reported that long non-coding RNA MALAT1 (lncRNA-MALAT1) highly expressed in endometriosis and up-regulated by hypoxia. Hypoxia may also induce autophagy, which might act as cell protective mechanism. However, the relationship between lncRNA-MALAT1 and autophagy under hypoxia conditions in endometriosis remains unknown. In the present study, we found that both lncRNA-MALAT1 and autophagy level were up-regulated in ectopic endometrium from patients with endometriosis, and its expression level correlates positively with that of hypoxia-inducible factor-1α (HIF-1α). In cultured human endometrial stromal cells, both lncRNA-MALAT1 and autophagy were induced by hypoxia in a time-dependent manner and lncRNA-MALAT1 up-regulation was dependent on HIF-1α signalling. Our analyses also show that knockdown of lncRNA-MALAT1 suppressed hypoxia induced autophagy. Furthermore, inhibiting autophagy with specific inhibitor 3-Methyladenine (3-MA) and Beclin1 siRNA enhanced apoptosis of human endometrial stromal cells under hypoxia condition. Collectively, our findings identify that lncRNA-MALAT1 mediates hypoxia-induced pro-survival autophagy of endometrial stromal cells in endometriosis.