Targeting of syndecan-1 by micro-ribonucleic acid miR-10b modulates invasiveness of endometriotic cells via dysregulation of the proteolytic milieu and interleukin-6 secretion.
Schneider C, Kässens N, Greve B, Hassan H, Schüring AN, Starzinski-Powitz A, Kiesel L, Seidler DG, Götte M
Research article (journal)Abstract
OBJECTIVE: To study the function of syndecan-1 (SDC1) and its potential regulator miR-10b in endometriosis. DESIGN: Experimental laboratory study. SETTING: University medical center. PATIENT(S): Not applicable. INTERVENTION(S): The human endometriotic cell line 12Z was transiently transfected with SDC1 small interfering RNA or miR-10b precursors and investigated for changes in cell behavior and gene expression. 12Z and primary eutopic endometrial stroma cells of two American Society for Reproductive Medicine class III endometriosis patients were transfected with miR-10b precursors to investigate posttranscriptional regulation of SDC1. MAIN OUTCOME MEASURE(S): Quantitative polymerase chain reaction, Western blotting, flow cytometry, 3' untranslated region luciferase assays, and zymography were used 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, cell viability assays, and mitogen-activated protein kinase activation blots. RESULT(S): Knockdown of SDC1 inhibited Matrigel invasiveness by >60% but did not affect cell viability. Interleukin-6 secretion, matrix metalloproteinase-9 expression, and matrix metalloproteinase-2 activity were reduced, whereas plasminogen activator inhibitor-1 protein expression was up-regulated. miR-10b overexpression significantly down-regulated SDC1, reduced Matrigel invasiveness by 20% and cell viability by 14%, and decreased mitogen-activated protein kinase activation in response to hepatocyte growth factor. CONCLUSION(S): Syndecan-1, a target of miR-10b, inhibits epithelial endometriotic cell invasiveness through down-regulation of metalloproteinase activity and interleukin-6.
Details about the publication
Authors from the University of Münster
| Götte, Martin | Department of Gynecology and Obstetrics |
| Kiesel, Ludwig | Department of Gynecology and Obstetrics |
| Schneider, Cornelia | Department of Gynecology and Obstetrics |
| Schüring, Andreas Norbert | Department of Gynecology and Obstetrics |
Promotionen, aus denen die Publikation resultiert
| Molecular functions of the heparan sulfate proteoglycan Syndecan-1 in the pathogenesis of endometrial diseases Candidate: Schneider, Cornelia | Supervisors: Götte, Martin; Liebau, Eva; Greve, Burkhard Period of time: 21/03/2011 - 11/03/2013 Doctoral examination procedure finished at: Doctoral examination procedure at University of Münster | |
| Dual roles of the heparan sulphate proteoglycan Syndecan-1 in cytokine- and integrin-mediated modulation of breast cancer stem cell function and motility Candidate: Hassan, Hebatallah Eshmawy Mohamed Mahgoub | Supervisors: Götte, Martin; Liebau, Eva; Greve, Burkhard Period of time: 07/12/2009 - 11/01/2013 Doctoral examination procedure finished at: Doctoral examination procedure at University of Münster | |
| Funktionelle Analyse von Zielgenen der mikroRNA miR-10b als Pathogenesefaktoren der Endometriose Candidate: Kässens, Nadja | Supervisors: Götte, Martin Period of time: 30/06/2010 - 30/07/2012 Doctoral examination procedure finished at: Doctoral examination procedure at University of Münster |