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

Kiener, Mirjam; Chen, Lanpeng; Krebs, Markus; Grosjean, Joël; Klima, Irena; Kalogirou, Charis; Riedmiller, Hubertus; Kneitz, Burkhard; Thalmann, George; Snaar-Jagalska, Ewa; Spahn, Martin; Kruithof-de Julio, Marianna; Zoni, Eugenio (2019). miR-221-5p regulates proliferation and migration in human prostate cancer cells and reduces tumor growth in vivo. BMC cancer, 19(1), p. 627. BioMed Central 10.1186/s12885-019-5819-6

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Urologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Urologie

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology

UniBE Contributor:

Kiener, Mirjam; Grosjean, Joël; Klima, Irena; Thalmann, George; Kruithof-de Julio, Marianna and Zoni, Eugenio

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

1471-2407

Publisher:

BioMed Central

Language:

English

Submitter:

Jeannine Wiemann

Date Deposited:

19 Aug 2019 11:34

Last Modified:

08 Nov 2019 08:01

Publisher DOI:

10.1186/s12885-019-5819-6

PubMed ID:

31238903

Uncontrolled Keywords:

Migration Proliferation Prostate cancer Tumor suppressor miRNA miR-221-5p

BORIS DOI:

10.7892/boris.132042

URI:

https://boris.unibe.ch/id/eprint/132042

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