PUBLICATION
miR-221-5p regulates proliferation and migration in human prostate cancer cells and reduces tumor growth in vivo
- Authors
- Kiener, M., Chen, L., Krebs, M., Grosjean, J., Klima, I., Kalogirou, C., Riedmiller, H., Kneitz, B., Thalmann, G.N., Snaar-Jagalska, E., Spahn, M., Kruithof-de Julio, M., Zoni, E.
- ID
- ZDB-PUB-190627-14
- Date
- 2019
- Source
- BMC cancer 19: 627 (Journal)
- Registered Authors
- Snaar-Jagalska, Ewa B.
- Keywords
- Migration, Proliferation, Prostate cancer, Tumor suppressor miRNA, miR-221-5p
- MeSH Terms
-
- Analysis of Variance
- Animals
- Cell Line, Tumor
- Cell Movement/genetics*
- Cell Proliferation/genetics*
- Down-Regulation
- Gene Knockdown Techniques
- Humans
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- MicroRNAs/genetics
- MicroRNAs/metabolism*
- Neoplasm Metastasis
- Prostate/metabolism
- Prostatic Neoplasms/metabolism*
- Prostatic Neoplasms/pathology*
- Transplantation, Heterologous
- Tumor Burden
- Tumor Stem Cell Assay
- Zebrafish
- PubMed
- 31238903 Full text @ BMC Cancer
Citation
Kiener, M., Chen, L., Krebs, M., Grosjean, J., Klima, I., Kalogirou, C., Riedmiller, H., Kneitz, B., Thalmann, G.N., Snaar-Jagalska, E., Spahn, M., Kruithof-de Julio, M., Zoni, E. (2019) miR-221-5p regulates proliferation and migration in human prostate cancer cells and reduces tumor growth in vivo. BMC cancer. 19:627.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping