Refine
Has Fulltext
- yes (9)
Is part of the Bibliography
- yes (9)
Document Type
- Journal article (9)
Language
- English (9)
Keywords
- prostate cancer (2)
- Bacillus-Calmette-Guerin (1)
- Biomarker (1)
- Biopsy (1)
- Calibration (1)
- Clinical prediction rule (1)
- False positive reactions (1)
- Hemospermia (1)
- Infection control (1)
- Kidney cancer (1)
- MAINZPouch (1)
- Metastatic melanoma (1)
- Methicillin-resistant staphylococcus aureus (1)
- MircoRNA (1)
- Predictive value of tests (1)
- Profiling (1)
- Prognosis (1)
- RCC (1)
- Renal cell carcinoma (1)
- Seminal vesicle tumor (1)
- Tumour markers (1)
- Ultrasound (1)
- biomarker (1)
- biomarkers (1)
- cancer surveillance (1)
- continence mechanism (1)
- continent cutaneous urinary diversion (1)
- forecasting (1)
- gene expression (1)
- gene targeting (1)
- high-risk prostate cancer (1)
- immune response (1)
- immunotherapy (1)
- kidneys (1)
- luciferase (1)
- metastasis (1)
- miR-126 (1)
- miR-205 (1)
- miR-21 (1)
- miR-221-5p (1)
- miRNA (1)
- microRNA (1)
- microarrays (1)
- migration (1)
- oncogenes (1)
- pouch (1)
- prognosis (1)
- proliferation (1)
- protein biomarkers (1)
- regression analysis (1)
- renal cancer (1)
- renal cell carcinoma (1)
- revisional surgery (1)
- surgical and invasive medical procedures (1)
- surgical oncology (1)
- system bcg (1)
- tumor cells (1)
- tumor suppressor miRNA (1)
- ubiquitin (1)
Institute
Sonstige beteiligte Institutionen
Background
Despite latest advances in prostate cancer (PCa) therapy, PCa remains the third-leading cause of cancer-related death in European men. Dysregulation of microRNAs (miRNAs), small non-coding RNA molecules with gene expression regulatory function, has been reported in all types of epithelial and haematological cancers. In particular, miR-221-5p alterations have been reported in PCa.
Methods
miRNA expression data was retrieved from a comprehensive publicly available dataset of 218 PCa patients (GSE21036) and miR-221-5p expression levels were analysed. The functional role of miR-221-5p was characterised in androgen- dependent and androgen- independent PCa cell line models (C4–2 and PC-3M-Pro4 cells) by miR-221-5p overexpression and knock-down experiments. The metastatic potential of highly aggressive PC-3M-Pro4 cells overexpressing miR-221-5p was determined by studying extravasation in a zebrafish model. Finally, the effect of miR-221-5p overexpression on the growth of PC-3M-Pro4luc2 cells in vivo was studied by orthotopic implantation in male Balb/cByJ nude mice and assessment of tumor growth.
Results
Analysis of microRNA expression dataset for human primary and metastatic PCa samples and control normal adjacent benign prostate revealed miR-221-5p to be significantly downregulated in PCa compared to normal prostate tissue and in metastasis compared to primary PCa. Our in vitro data suggest that miR-221-5p overexpression reduced PCa cell proliferation and colony formation. Furthermore, miR-221-5p overexpression dramatically reduced migration of PCa cells, which was associated with differential expression of selected EMT markers. The functional changes of miR-221-5p overexpression were reversible by the loss of miR-221-5p levels, indicating that the tumor suppressive effects were specific to miR-221-5p. Additionally, miR-221-5p overexpression significantly reduced PC-3M-Pro4 cell extravasation and metastasis formation in a zebrafish model and decreased tumor burden in an orthotopic mouse model of PCa.
Conclusions
Together these data strongly support a tumor suppressive role of miR-221-5p in the context of PCa and its potential as therapeutic target.