Open AccessLong non‐coding RNA MALAT 1 mediates hypoxia‐induced pro‐survival autophagy of endometrial stromal cells in endometriosis
Author(s) -
Liu Hengwei,
Zhang Zhibing,
Xiong Wenqian,
Zhang Ling,
Du Yu,
Liu Yi,
Xiong Xingao
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13947
Subject(s) - autophagy , hypoxia (environmental) , stromal cell , endometriosis , rna , cancer research , long non coding rna , biology , small interfering rna , microbiology and biotechnology , circular rna , apoptosis , chemistry , medicine , gene , biochemistry , organic chemistry , oxygen
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 MALAT 1 (lnc RNA ‐ MALAT 1) 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 lnc RNA ‐ MALAT 1 and autophagy under hypoxia conditions in endometriosis remains unknown. In the present study, we found that both lnc RNA ‐ MALAT 1 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 lnc RNA ‐ MALAT 1 and autophagy were induced by hypoxia in a time‐dependent manner and lnc RNA ‐ MALAT 1 up‐regulation was dependent on HIF ‐1α signalling. Our analyses also show that knockdown of lnc RNA ‐ MALAT 1 suppressed hypoxia induced autophagy. Furthermore, inhibiting autophagy with specific inhibitor 3‐Methyladenine (3‐ MA ) and Beclin1 si RNA enhanced apoptosis of human endometrial stromal cells under hypoxia condition. Collectively, our findings identify that lnc RNA ‐ MALAT 1 mediates hypoxia‐induced pro‐survival autophagy of endometrial stromal cells in endometriosis.