Objective: Hypoxia may play a role in the survival of ectopic endometrial cells. This study aimed to explore how hypoxia responsive miR-210 is involved in cell survival and autophagic response of endometriotic cells.
Materials and methods: The expression of hypoxia-inducible factor 1-alpha (HIF-1α) and miR-210 in eutopic and ectopic endometrial tissues were measured. The expression changes of HIF-1α and miR-210 in ovarian endometriotic cell line CRL-7566 after hypoxic culture were further explored. The influence of miR-210 on cell viability and apoptosis was quantified using CCK-8 assay and flow cytometry analysis. The effect of miR-210 on Bcl-2 expression and the effect of miR-210/Bcl-2 axis on autophagy in the cells were measured by Western blot analysis.
Results: Ectopic lesion had stronger HIF-1α positive signals, as well as more HIF-1α positive cells per visual field than the eutopic endometrium. MiR-210 expression was also elevated in the ectopic lesions. In in-vitro models, CRL-7566 cells had significantly higher expression of HIF-1α and miR-210 after hypoxic treatment. MiR-210 overexpression partly preserved cell viability in hypoxia, while miR-210 knockdown facilitated the loss of cell viability. In addition, miR-210 significantly attenuated hypoxia-induced apoptosis in CRL-7566 cells. Enforced miR-210 overexpression significantly promoted autophagy in hypoxia. Knockdown of endogenous Bcl-2 significantly enhanced autophagy, the effect of which was similar to that of miR-210.
Conclusions: The hypoxia-induced higher miR-210 expression may contribute to pathological development of endometriosis at least through enhancing cell survival and promoting autophagy via Bcl2/Beclin-1 axis.