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BMC Cancer
Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Prostate Cancer | Research article

miR-221-5p regulates proliferation and migration in human prostate cancer cells and reduces tumor growth in vivo

Authors: Mirjam Kiener, Lanpeng Chen, Markus Krebs, Joël Grosjean, Irena Klima, Charis Kalogirou, Hubertus Riedmiller, Burkhard Kneitz, George N. Thalmann, Ewa Snaar-Jagalska, Martin Spahn, Marianna Kruithof-de Julio, Eugenio Zoni

Published in: BMC Cancer | Issue 1/2019

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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.
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Metadata
Title
miR-221-5p regulates proliferation and migration in human prostate cancer cells and reduces tumor growth in vivo
Authors
Mirjam Kiener
Lanpeng Chen
Markus Krebs
Joël Grosjean
Irena Klima
Charis Kalogirou
Hubertus Riedmiller
Burkhard Kneitz
George N. Thalmann
Ewa Snaar-Jagalska
Martin Spahn
Marianna Kruithof-de Julio
Eugenio Zoni
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-019-5819-6

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