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J Cell Mol Med. 2019 Jan;23(1):439-452. doi: 10.1111/jcmm.13947. Epub 2018 Oct 15.

Long non-coding RNA MALAT1 mediates hypoxia-induced pro-survival autophagy of endometrial stromal cells in endometriosis.

Author information

1
Department of Obstetrics and Gynecology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.
2
Department of Physiology, Wayne State University, Detroit, Michigan.
3
Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan.
4
Department of Ear-Nose-Throat (ENT), Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.

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.

KEYWORDS:

HIF-1α; apoptosis; autophagy; endometriosis; hypoxia; lncRNA-MALAT1

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