title: Hypoxia responsive miR-210 promotes cell survival and autophagy of endometriotic cells in hypoxia.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Gynecology and Obstetrics, the Central Hospital of Binzhou, Binzhou, Shandong, China. yxr0204@163.com.
authors.forename: T-X
authors.initials: TX
authors.lastname: Xu
authors.forename: S-Z
authors.initials: SZ
authors.lastname: Zhao
authors.forename: M
authors.initials: M
authors.lastname: Dong
authors.forename: X-R
authors.initials: XR
authors.lastname: Yu
mesh_terms: D017209:Apoptosis; D001343:Autophagy / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D015687:Cell Hypoxia / Q000235:genetics* / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D004715:Endometriosis / Q000378:metabolism; D004717:Endometrium / Q000166:cytology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C543800:MIRN210 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2