Dataset Information

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

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.

SUBMITTER: Kiener M

PROVIDER: S-EPMC6593572 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Kiener Mirjam M Chen Lanpeng L Krebs Markus M Grosjean Joël J Klima Irena I Kalogirou Charis C Riedmiller Hubertus H Kneitz Burkhard B Thalmann George N GN Snaar-Jagalska Ewa E Spahn Martin M Kruithof-de Julio Marianna M Zoni Eugenio E

BMC cancer 20190625 1

<h4>Background</h4>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.<h4>Methods</h4>miRNA expression data was retrieved from a comprehensive publicly available dataset ...[more]

PMID: 31238903

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