title: microRNAs expression in endometriosis and their relation to angiogenic factors.
abstract: BACKGROUND
  Endometriosis is a common, multifactorial disease in which angiogenesis may be involved in the growth of endometrium outside the uterus. microRNAs (miRNAs) are 21-22 nucleotide non-coding RNAs that regulate gene expression and play fundamental roles in biological processes. The objective of this study was to analyze several miRNAs related to angiogenesis and the angiogenic factors, vascular endothelial growth factor-A (VEGF-A) and thrombospondin-1 (TSP-1), in endometriotic lesions (ovarian endometrioma, peritoneal lesion and rectovaginal nodule) and eutopic endometrium from women with endometriosis.
  
  
  METHODS
  TaqMan real-time PCR was used to assess the expression of the miRNAs (miR-15b, -16, -17-5p, -20a, -21, -125a, -221 and -222), while VEGF-A and TSP-1 mRNA were assessed by real-time PCR, with SYBR Green I and VEGF-A and TSP-1 protein levels were quantified by ELISA. Included in the study were 58 women with endometriosis and 38 control women.
  
  
  RESULTS
  In paired samples, ovarian endometrioma showed significantly lower VEGF-A mRNA (P = 0.02) and protein (P = 0.002) expression than eutopic endometrium and higher expression of miR-125a (P = 0.003) and miR-222 (P <0.001). However, ovarian endometrioma had significantly higher expression of the angiogenic inhibitor TSP-1 and lower expression of miR-17-5p than eutopic endometrium (P < 0.001). Moreover, a significant inverse correlations between miR-222 and VEGF-A protein levels (-0.267, P = 0.018) and between miR-17-5p and TSP-1 protein levels (-0.260, P=0.022) were observed. Peritoneal lesions showed a significant increase in VEGF-A in comparison with ovarian endometrioma (P < 0.01).
  
  
  CONCLUSIONS
  Expression levels of miRNAs related to angiogenesis were different in eutopic endometrium from that observed in ovarian endometrioma. This could influence the expression of angiogenic factors and play a role in the pathogenesis of endometriosis.
authors.affiliation: Research Center, Hospital Universitario La Fe, Valencia, Spain.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Ramón
authors.forename: Aitana
authors.initials: A
authors.lastname: Braza-Boïls
authors.forename: Juan
authors.initials: J
authors.lastname: Gilabert-Estellés
authors.forename: Juan
authors.initials: J
authors.lastname: Gilabert
authors.forename: Francisco
authors.initials: F
authors.lastname: España
authors.forename: Melitina
authors.initials: M
authors.lastname: Chirivella
authors.forename: Amparo
authors.initials: A
authors.lastname: Estellés
mesh_terms: D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D004715:Endometriosis / Q000235:genetics* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008597:Menstrual Cycle / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D035683:MicroRNAs; D012333:RNA, Messenger; D019700:Thrombospondin 1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A