{"paper_id":"ea10f309-7078-43a9-8aa6-51ef49414493","body_text":"Subscribe to RSS\nDOI: 10.1055/s-0033-1336719\nTargeting of Syndecan-1 by microRNA miR-10b modulates invasiveness of endometriotic cells via dysregulation of IL-6 secretion and MAPK signaling\nmicroRNAs are small non-coding RNAs which regulate gene expression at the posttranscriptional and translational level. microRNAs have previously been demonstrated to be dysregulated in endometriosis, a hormone-dependent disease associated with reduced fertility. One of the dysregulated microRNAs is miR-10b, however, its function has not been addressed at the molecular level. Here, we aimed at elucidating the function of the heparan sulfate proteoglycan Syndecan-1 and its potential regulator miR-10b in endometriosis. for this purpose, the human endometriotic cell line 12Z was transiently transfected with Syndecan-1 (SDC1) siRNA or miR-10b precursors and investigated for changes in cell behavior and gene expression. 12Z and primary eutopic endometrial stroma cells of two ASRM-III endometriosis patients were transfected with miR-10b precursors to investigate posttranscriptional regulation of SDC1. qPCR, Western blotting, flow cytometry, 3'UTR luciferase assays and zymography were employed to measure miR-10b-dependent targeting of SDC1, and SDC1-dependent expression changes of proteases and interleukin-6. Altered cell behavior was monitored by matrigel invasion assays, MTT cell viability assays and mitogen activated protein kinase (MAPK) activation blots. Our data showed that SDC1 knockdown inhibited matrigel invasiveness by > 60%, but did not affect cell viability. Interleukin-6 secretion, MMP-9 expression and MMP-2 activity were reduced, while PAI-1 protein expression was upregulated. miR-10b overexpression significantly downregulated SDC1, reduced matrigel invasiveness by 20%, and cell viability by 14%, and decreased MAPK activation in response to hepatocyte growth factor. We conclude that SDC1, a novel target of miR-10b, inhibits epithelial endometriotic cell invasiveness through downregulation of metalloproteinase activity and interleukin-6.","source_license":"CC0","license_restricted":false}