title: MicroRNA-205, a novel regulator of the anti-apoptotic protein Bcl2, is downregulated in prostate cancer.
abstract: Decreased expression of the microRNA miR-205 has been observed in multiple tumour types due to its role in the epithelial to mesenchymal transition, which promotes metastasis. We determined the expression of miR-205 in 111 archival samples of prostate carcinoma and found it to be strongly reduced in most samples, with a median expression level of 16% in comparison to benign tissue from the same patient. Lower miR-205 expression correlated significantly with tumour size and miR-205 levels decreased with increasing Gleason score from 7a=3+4 to 8=4+4. In addition, we describe the anti-apoptotic protein BCL2 as a target of miR-205, relevant for prostate cancer due to its role in prognosis of primary tumours and in the appearance of androgen independence. The repression of BCL2 by miR-205 was confirmed using reporter assays and western blotting. BCL2 mRNA expression in the same collective of prostate cancer tissue samples was associated with higher Gleason score and extracapsular extension of the tumour (pT3). Consistent with its anti-apoptotic target BCL2, miR-205 promoted apoptosis in prostate cancer cells in response to DNA damage by cisplatin and doxorubicin in the prostate cancer cell lines PC3 and LnCap. MiR-205 also inhibited proliferation in these cell lines.
authors.affiliation: Institute of Pathology, Ruhr-University Bochum, D-44789 Bochum, Germany.
authors.forename: Berlinda
authors.initials: B
authors.lastname: Verdoodt
authors.forename: Matthias
authors.initials: M
authors.lastname: Neid
authors.forename: Markus
authors.initials: M
authors.lastname: Vogt
authors.forename: Viktoria
authors.initials: V
authors.lastname: Kuhn
authors.forename: Sven-Thorsten
authors.initials: ST
authors.lastname: Liffers
authors.forename: Rein-Jüri
authors.initials: RJ
authors.lastname: Palisaar
authors.forename: Joachim
authors.initials: J
authors.lastname: Noldus
authors.forename: Andrea
authors.initials: A
authors.lastname: Tannapfel
authors.forename: Alireza
authors.initials: A
authors.lastname: Mirmohammadsadegh
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D060787:Neoplasm Grading; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism
chemical_list: D002945:Cisplatin; D004317:Doxorubicin; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; C534425:MIR205, human