Journal article
Epigenetic-induced repression of microRNA-205 is associated with MED1 activation and a poorer prognosis in localized prostate cancer
Oncogenesis, Vol.32(23), pp.2891-2899
2013
Abstract
Deregulation of microRNA (miRNA) expression can have a critical role in carcinogenesis. Here we show in prostate cancer that miRNA-205 (miR-205) transcription is commonly repressed and the MIR-205 locus is hypermethylated. LOC642587, the MIR-205 host gene of unknown function, is also concordantly inactivated. We show that miR-205 targets mediator 1 (MED1, also called TRAP220 and PPARBP) for transcriptional silencing in normal prostate cells, leading to reduction in MED1 mRNA levels, and in total and active phospho-MED1 protein. Overexpression of miR-205 in prostate cancer cells negatively affects cell viability, consistent with a tumor suppressor function. We found that hypermethylation of the MIR-205 locus was strongly related with a decrease in miR-205 expression and an increase in MED1 expression in primary tumor samples (n=14), when compared with matched normal prostate (n=7). An expanded patient cohort (tumor n=149, matched normal n=30) also showed significant MIR-205 DNA methylation in tumors compared with normal, and MIR-205 hypermethylation is significantly associated with biochemical recurrence (hazard ratio=2.005, 95% confidence interval (1.109, 3.625), P=0.02), in patients with low preoperative prostate specific antigen. In summary, these results suggest that miR-205 is an epigenetically regulated tumor suppressor that targets MED1 and may provide a potential biomarker in prostate cancer management.
Details
- Title
- Epigenetic-induced repression of microRNA-205 is associated with MED1 activation and a poorer prognosis in localized prostate cancer
- Authors/Creators
- T. Hulf (Author/Creator) - Garvan Institute of Medical ResearchT. Sibbritt (Author/Creator) - Garvan Institute of Medical ResearchE.D. Wiklund (Author/Creator) - Aarhus UniversityK. Patterson (Author/Creator) - Garvan Institute of Medical ResearchJ.Z. Song (Author/Creator) - Garvan Institute of Medical ResearchC. Stirzaker (Author/Creator) - Garvan Institute of Medical ResearchW. Qu (Author/Creator) - Garvan Institute of Medical ResearchS. Nair (Author/Creator) - Garvan Institute of Medical ResearchL.G. Horvath (Author/Creator) - Royal Prince Alfred HospitalN.J. Armstrong (Author/Creator) - Garvan Institute of Medical ResearchJ.G. Kench (Author/Creator) - Royal Prince Alfred HospitalR.L. Sutherland (Author/Creator) - Garvan Institute of Medical ResearchS.J. Clark (Author/Creator) - Garvan Institute of Medical Research
- Publication Details
- Oncogenesis, Vol.32(23), pp.2891-2899
- Publisher
- Nature Publishing Group
- Identifiers
- 991005542198807891
- Copyright
- © 2013 Macmillan Publishers Limited
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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Source: InCites
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.196 Micro & Long Noncoding RNA
- 1.196.68 MicroRNA in Cancer
- Web Of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- Genetics & Heredity
- Oncology
- ESI research areas
- Molecular Biology & Genetics