Uterine leiomyosarcoma and endometrial stromal sarcoma have unique miRNA signatures

• microRNA array analysis differentiates uterine endometrial stromal sarcoma from leiomyosarcoma.
• microRNAs are predominantly underexpressed in metastatic compared to primary leiomyosarcoma.
• Frizzled-6 silencing suppresses invasion in leiomyosarcoma cells in vitro.

ObjectiveTo 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.MethodsEight 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.ResultsNinety-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.ConclusionsDifferential 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.