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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Prognostic significance of Dicer expression in ovarian cancer - Link to global microRNA changes and oestrogen receptor expression
Journal of Pathology, Volume 220, No. 3, Year 2010
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Description
MicroRNA (miRNA) deregulation is a hallmark of human cancer. However, the mechanisms underlying miRNA alteration and the specific role of proteins involved in miRNA processing remains to be elucidated. Dicer is a key enzyme in the miRNA processing pathway that is essential for the production of mature miRNAs from their precursors. We tested the hypothesis that Dicer has biological and clinical relevance in ovarian cancer, using a range of methods including in vitro manipulation of Dicer expression. We observed down-regulation of Dicer in a subgroup of ovarian carcinomas, and found that decreased Dicer expression correlates significantly with reduced patient survival in serous cancers and advanced disease stages. Moreover, microarray and functional analysis suggest that reduced Dicer expression is connected with a global down-regulation of the microRNAome and with gene expression changes, particularly reduced expression of oestrogen receptor (ER) mRNA and protein in tumour tissue and in cell culture. Our data suggest a common mechanism for miRNAs changes by alterations in the basic machinery controlling miRNA biogenesis, of which Dicer is a central enzyme. These alterations of miRNA processing are of prognostic value and may play a role in the molecular pathogenesis of ovarian carcinoma and, possibly, other tumours. Knowledge of these molecular pathways may help toward new targeted therapeutic approaches for ovarian cancer. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Authors & Co-Authors
Faggad, Areeg
Germany, Berlin
Charité – Universitätsmedizin Berlin
Sudan, Wad Medani
University of Gezira
Budczies, Jan
Germany, Berlin
Charité – Universitätsmedizin Berlin
Tchernitsa, Oleg I.
Germany, Berlin
Charité – Universitätsmedizin Berlin
Darb-Esfahani, Silvia
Germany, Berlin
Charité – Universitätsmedizin Berlin
Sehouli, Jalid
Germany, Berlin
Charité – Universitätsmedizin Berlin
Müller, Berit Maria
Germany, Berlin
Charité – Universitätsmedizin Berlin
Wirtz, Ralph Markus
Germany, Munich
Siemens ag
Chekerov, Radoslav
Germany, Berlin
Charité – Universitätsmedizin Berlin
Weichert, Wilko
Germany, Berlin
Charité – Universitätsmedizin Berlin
Sinn, Bruno Valentin
Germany, Berlin
Charité – Universitätsmedizin Berlin
Mucha, Christin
Germany, Berlin
Charité – Universitätsmedizin Berlin
Elwali, Nasr Eldin
Sudan, Wad Medani
University of Gezira
Schäfer, Reinhold
Germany, Berlin
Charité – Universitätsmedizin Berlin
Dietel, Manfred
Germany, Berlin
Charité – Universitätsmedizin Berlin
Denkert, Carsten
Germany, Berlin
Charité – Universitätsmedizin Berlin
Statistics
Citations: 94
Authors: 15
Affiliations: 3
Identifiers
Doi:
10.1002/path.2658
ISSN:
00223417
e-ISSN:
10969896
Research Areas
Cancer
Genetics And Genomics
Health System And Policy