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MicroRNA expression signature of castration-resistant prostate cancer: the microRNA-221/222 cluster functions as a tumour suppressor and disease progression marker
- Source :
- British Journal of Cancer
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
Abstract
- Background: Our present study of the microRNA (miRNA) expression signature in castration-resistant prostate cancer (CRPC) revealed that the clustered miRNAs microRNA-221 (miR-221) and microRNA-222 (miR-222) are significantly downregulated in cancer tissues. The aim of this study was to investigate the functional roles of miR-221 and miR-222 in prostate cancer (PCa) cells. Methods: A CRPC miRNA signature was constructed by PCR-based array methods. Functional studies of differentially expressed miRNAs were analysed using PCa cells. The association between miRNA expression and overall survival was estimated by the Kaplan–Meier method. In silico database and genome-wide gene expression analyses were performed to identify molecular targets regulated by the miR-221/222 cluster. Results: miR-221 and miR-222 were significantly downregulated in PCa and CRPC specimens. Kaplan–Meier survival curves showed that low expression of miR-222 predicted a short duration of progression to CRPC. Restoration of miR-221 or miR-222 in cancer cells revealed that both miRNAs significantly inhibited cancer cell migration and invasion. Ecm29 was directly regulated by the miR-221/222 cluster in PCa cells. Conclusions: Loss of the tumour-suppressive miR-221/222 cluster enhanced migration and invasion in PCa cells. Our data describing targets regulated by the tumour-suppressive miR-221/222 cluster provide insights into the mechanisms of PCa and CRPC progression.
- Subjects :
- Male
Cancer Research
tumour suppressor
expression signature
Expression Signature
Down-Regulation
urologic and male genital diseases
Bioinformatics
Disease cluster
law.invention
Prostate cancer
Downregulation and upregulation
Cell Movement
law
Cell Line, Tumor
microRNA
Biomarkers, Tumor
medicine
Humans
castration-resistant prostate cancer
Molecular Diagnostics
Survival analysis
Ecm29
business.industry
Disease progression
Prognosis
prostate cancer
miR-222
medicine.disease
Survival Analysis
miR-221
Gene Expression Regulation, Neoplastic
MicroRNAs
Prostatic Neoplasms, Castration-Resistant
Oncology
Multigene Family
Disease Progression
Cancer research
Suppressor
business
Subjects
Details
- ISSN :
- 15321827 and 00070920
- Volume :
- 113
- Database :
- OpenAIRE
- Journal :
- British Journal of Cancer
- Accession number :
- edsair.doi.dedup.....a8447dac951c66cb6f7ab67f59dba88c