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

Syndecan-1 inhibits invasiveness of epithelial endometriotic cells by modulating matrix metalloproteinases MMP-2 and MMP-9, plasminogen activator inhibitor-1, and interleukin-6 and is regulated by the microRNA miR-10b, both possible novel targets for therapeutic approaches.

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Authors

Cornelia Schneider, M.Sc., Nadja Kässens, M.D., Burkhard Greve, Ph.D., Hebatallah Hassan, M.Sc., Andreas Schüring, M.D., Anna Starzinski-Powitz, Ph.D., Ludwig Kiesel, M.D.,Ph.D., Daniela G. Seidler, Ph.D., Martin Götte, Ph.D.

Volume 99, Issue 3, Pages 871-881.e1, 1 March 2013

Abstract

Objective:

To study the function of Syndecan-1 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 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.

Main Outcome Measure(s):

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.

Result(s):

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.

Conclusion(s):

SDC1, a target of miR-10b, inhibits epithelial endometriotic cell invasiveness through downregulation of metalloproteinase activity and interleukin-6.

Read the full text at: http://www.fertstert.org/article/S0015-0282(12)02399-0/fulltext


Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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