title: Uterine leiomyosarcoma and endometrial stromal sarcoma have unique miRNA signatures.
abstract: OBJECTIVE
  To compare the microRNA (miRNA) profiles of uterine endometrial stromal sarcoma (ESS) and leiomyosarcoma (LMS), and to compare the miRNA signatures of primary and metastatic uterine LMS.
  
  
  METHODS
  Eight primary LMS, 9 primary ESS and 8 metastatic LMS were analyzed for miRNA profiles using TaqMan Human miRNA Array Cards. Findings for 20 differentially expressed miRNAs were validated in a series of 44 uterine sarcomas (9 primary uterine ESS, 17 primary uterine LMS, 18 metastatic LMS) using qPCR. Frizzled-6 protein expression was analyzed in 30 LMS (15 primary, 15 metastases). Frizzled-6 was silenced in SK-LMS-1 uterine LMS cells using siRNA and the effect on invasion, wound healing and matrix metalloproteinase-2 (MMP2) activity was assessed.
  
  
  RESULTS
  Ninety-four miRNAs were significantly differentially expressed in ESS and LMS, of which 76 were overexpressed in ESS and 18 overexpressed in LMS. Forty-nine miRNAs were differentially expressed in primary and metastatic LMS, of which 45 were overexpressed in primary LMS and 4 in metastases. Differential expression was confirmed for 10/20 miRNA analyzed using qPCR. Frizzled-6 silencing in SK-LMS-1 cells significantly inhibited cellular invasion, wound healing and MMP-2 activity.
  
  
  CONCLUSIONS
  Differential miRNA signatures of ESS and LMS provide novel data regarding transcriptional regulation in these cancers, based on which new potential diagnostic markers, prognostic biomarkers and therapeutic targets may be explored. Differences in miRNA profiles of primary and metastatic LMS may improve our understanding of disease progression in this aggressive malignancy.
authors.affiliation: Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors.forename: Yeheli
authors.initials: Y
authors.lastname: Ravid
authors.affiliation: Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors.forename: Malka
authors.initials: M
authors.lastname: Formanski
authors.affiliation: Genomic Data Analysis Unit, Hadassah Medical School, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Smith
authors.affiliation: Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel. Electronic address: reich@cc.huji.ac.il.
authors.forename: Reuven
authors.initials: R
authors.lastname: Reich
authors.affiliation: Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo, Norway; The Medical Faculty, University of Oslo, N-0316 Oslo, Norway. Electronic address: bend@medisin.uio.no.
authors.forename: Ben
authors.initials: B
authors.lastname: Davidson
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D051157:Frizzled Receptors / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D007890:Leiomyosarcoma / Q000235:genetics* / Q000556:secondary*; D035683:MicroRNAs / Q000032:analysis*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D018203:Sarcoma, Endometrial Stromal / Q000235:genetics* / Q000556:secondary*
chemical_list: C484687:FZD6 protein, human; D051157:Frizzled Receptors; D035683:MicroRNAs
keywords: Differential diagnosis; Endometrial stromal sarcoma; Leiomyosarcoma; MicroRNA; Tumor progression