title: MicroRNA-15b regulates reversion-inducing cysteine-rich protein with Kazal motifs (RECK) expression in human uterine leiomyoma.
abstract: BACKGROUND
  Human uterine leiomyoma (fibroids; LYO) are the most common benign neoplasms in reproductive-aged women. Dysregulated extracellular matrix and irregular LYO reversion-inducing cysteine-rich protein with Kazal motifs (RECK) expression are thought to be mediated by aberrant microRNA (miR) expression. The relationship of miR-15b and RECK expression in LYO has not been studied.
  
  
  METHODS
  The expression levels of miR-15b and RECK were determined by quantitative RT-PCR, Western blot, and immunohistochemistry in cultures derived from commercial primary leiomyoma (cpLYO) and myometrial (cpMYO) cell lines and leiomyoma (pLYO) and myometrium (pMYO) tissue from surgical samples respectively. The relationship between miR-15b and RECK expression in cpLYO and pLYO (compared to their respective myometrial controls) was evaluated following transfection of cell cultures with either miR-15b mimic or inhibitor.
  
  
  RESULTS
  Elevated levels of miR-15b were observed in cpLYO (2.82-fold; p = 0.04) and pLYO cell (1.30-fold; p = 0.0001) cultures respectively compared to corresponding MYO cell controls. Following transfection with miR-15b mimic, cpLYO cells (0.62-fold; p < 0.0001) and pLYO cells (0.68-fold; p < 0.0001) demonstrated reduced RECK protein expression. Following transfection with miR-15b inhibitor, cpLYO cells (1.20-fold; p < 0.0001) and pLYO cells (1.31-fold; p = 0.0007) demonstrated elevated RECK protein expression. RECK protein expression was reduced in pLYO tissues (0.73-fold; p < 0.0001) and pLYO (0.47-fold; p = 0.047) cells when compared to the corresponding MYO tissue controls.
  
  
  CONCLUSIONS
  Our findings suggest that miR-15b negatively regulates RECK expression in LYO, and increased miR-15b and decreased RECK expression may contribute to the pathobiology of LYO. The functional significance of miR-15b and RECK expression warrants further investigation as potential therapeutic targets for the treatment of human LYO.
authors.affiliation: Center for Reproductive Medicine, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China.|Vincent Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Their 9, 55 Fruit Street, Boston, MA, 02114, USA.
authors.forename: Yichun
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Vincent Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Their 9, 55 Fruit Street, Boston, MA, 02114, USA.
authors.forename: Lankai
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, MA, 02114, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Zukerberg
authors.affiliation: Vincent Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Their 9, 55 Fruit Street, Boston, MA, 02114, USA. brueda@mgh.harvard.edu.|Departments of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, MA, 02115, USA. brueda@mgh.harvard.edu.
authors.forename: Bo R
authors.initials: BR
authors.lastname: Rueda
authors.affiliation: Vincent Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Their 9, 55 Fruit Street, Boston, MA, 02114, USA. astyer@mgh.harvard.edu.|Departments of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, MA, 02115, USA. astyer@mgh.harvard.edu.
authors.forename: Aaron K
authors.initials: AK
authors.lastname: Styer
mesh_terms: D002460:Cell Line; D005260:Female; D058851:GPI-Linked Proteins / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007889:Leiomyoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D058851:GPI-Linked Proteins; C505361:MIRN15 microRNA, human; D035683:MicroRNAs; C115460:RECK protein, human
keywords: Fibroids; Myometrium; RECK; Uterine leiomyoma; miR-15b