title: MicroRNA 135 regulates HOXA10 expression in endometriosis.
abstract: BACKGROUND
  Homeo box A10 (HOXA10) regulates endometrial receptivity and its expression is decreased in women with endometriosis. Although sex steroids regulate HOXA10, these hormones are unaltered in endometriosis. We hypothesized a role for microRNA in the regulation of HOXA10.
  
  
  OBJECTIVE
  MicroRNA 135a and -b are small noncoding RNA with predicted targets that include HOXA10. We evaluated miR135a/b expression and HOXA10 regulation in endometrium from subjects with and without endometriosis.
  
  
  METHODS
  The design of the study was the measurement of miR135a/b expression by quantitative PCR and in vitro analysis of HOXA10 regulation.
  
  
  METHODS
  The study was conducted at a university medical center.
  
  
  METHODS
  Patients included 50 controls and 32 women with endometriosis.
  
  
  METHODS
  Study interventions included endometrial biopsies and in vitro transfection.
  
  
  METHODS
  miR135a/b and HOXA10 expression were measured in the study.
  
  
  RESULTS
  All endometrial samples expressed miR135a and -b. miR135a expression in controls was increased during the proliferative phase, decreased at the time of ovulation, and increased during the luteal phase. Subjects with endometriosis had 3-fold higher expression of miR135a in the proliferative phase than controls. miR135b showed less variation across the menstrual cycle; however, it was significantly increased in women with endometriosis in the proliferative and secretory phases. HOXA10 expression was simultaneously repressed in the endometrium of women with endometriosis. Transfection of endometrial stromal cells with mir135a/b or miR135a/b inhibitors resulted in the altered expression of HOXA10 mRNA and protein. miR135a or -b decreased luciferase expression driven by the HOXA10 3' untranslated region containing the miR135 binding site. miR135a regulation of HOXA10 was absent in MCF-7 cells, demonstrating cell specificity.
  
  
  CONCLUSIONS
  HOXA10 was aberrantly regulated in the endometrium of women with endometriosis by both miR135a and miR135b. Increased microRNA expression likely suppresses genes required for implantation.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA.
authors.forename: Rafaella
authors.initials: R
authors.lastname: Petracco
authors.forename: Olga
authors.initials: O
authors.lastname: Grechukhina
authors.forename: Shota
authors.initials: S
authors.lastname: Popkhadze
authors.forename: Efi
authors.initials: E
authors.lastname: Massasa
authors.forename: Yuping
authors.initials: Y
authors.lastname: Zhou
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Taylor
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D010064:Embryo Implantation / Q000235:genetics; D004715:Endometriosis / Q000235:genetics* / Q000378:metabolism; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008597:Menstrual Cycle / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D017154:Stromal Cells / Q000378:metabolism
chemical_list: D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; C544965:MIRN135 microRNA, human; D035683:MicroRNAs; C069634:HOXA10 protein, human