The tumour suppressor miR-34c targets MET in prostate cancer cells.
Author
Summary, in English
Background:The microRNA, miR-34c, is a well-established regulator of tumour suppression. It is downregulated in most forms of cancers and inhibits malignant growth by repressing genes involved in processes such as proliferation, anti-apoptosis, stemness, and migration. We have previously reported downregulation and tumour suppressive properties for miR-34c in prostate cancer (PCa).Methods:In this study, we set out to further characterize the mechanisms by which miR-34c deregulation contributes to PCa progression. The genes regulated by miR-34c in the PCa cell line PC3 were identified by microarray analyses and were found to be enriched in cell death, cell cycle, cellular growth, and cellular movement pathways. One of the identified targets was MET, a receptor tyrosine kinase activated by hepatocyte growth factor, that is crucial for metastatic progression.Results:We confirmed the inhibitory effect of miR-34c on both MET transcript and protein levels. The binding of miR-34c to two binding sites in the 3'-UTR of MET was validated using luciferase reporter assays and target site blockers. The effect of this regulation on the miR-34c inhibition of the migratory phenotype was also confirmed. In addition, a significant inverse correlation between miR-34c expression levels and MET immunostaining was found in PCa patients.Conclusion:These findings provide a novel molecular mechanism of MET regulation in PCa and contribute to the increasing evidence that miR-34c has a key tumour suppressive role in PCa.British Journal of Cancer advance online publication, 6 August 2013; doi:10.1038/bjc.2013.449 www.bjcancer.com.
Department/s
- Clinical Chemistry, Malmö
- Urological cancer, Malmö
- Department of Translational Medicine
- Medical Molecular Biology
- EpiHealth: Epidemiology for Health
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publishing year
2013
Language
English
Pages
1271-1278
Publication/Series
British Journal of Cancer
Volume
109
Issue
5
Full text
- Available as PDF - 57 MB
- Download statistics
Links
Document type
Journal article
Publisher
Nature Publishing Group
Topic
- Cancer and Oncology
Status
Published
Research group
- Clinical Chemistry, Malmö
- Urological cancer, Malmö
- Medical Molecular Biology
ISBN/ISSN/Other
- ISSN: 1532-1827