title: Prognostic significance of Dicer expression in ovarian cancer-link to global microRNA changes and oestrogen receptor expression.
abstract: 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.
authors: Institute of Pathology, Charité University Hospital, 10117 Berlin, Germany.
authors: Areeg
authors: A
authors: Faggad
authors: Jan
authors: J
authors: Budczies
authors: Oleg
authors: O
authors: Tchernitsa
authors: Silvia
authors: S
authors: Darb-Esfahani
authors: Jalid
authors: J
authors: Sehouli
authors: Berit M
authors: BM
authors: Müller
authors: Ralph
authors: R
authors: Wirtz
authors: Radoslav
authors: R
authors: Chekerov
authors: Wilko
authors: W
authors: Weichert
authors: Bruno
authors: B
authors: Sinn
authors: Christin
authors: C
authors: Mucha
authors: Nasr E
authors: NE
authors: Elwali
authors: Reinhold
authors: R
authors: Schäfer
authors: Manfred
authors: M
authors: Dietel
authors: Carsten
authors: C
authors: Denkert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D055785:Gene Knockdown Techniques; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics; D011960:Receptors, Estrogen / Q000378:metabolism*; D043244:Ribonuclease III / Q000378:metabolism*; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen; D043244:Ribonuclease III