MicroRNA-21 suppression impedes medulloblastoma cell migration

Grunder, Eveline; D'Ambrosio, Rocco; Fiaschetti, Giulio; Abela, Lucia; Arcaro, Alexandre; Zuzak, Tycho; Ohgaki, Hiroko; Lv, Sheng-Qing; Shalaby, Tarek; Grotzer, Michael (2011). MicroRNA-21 suppression impedes medulloblastoma cell migration. European journal of cancer, 47(16), pp. 2479-90. Amsterdam: Elsevier 10.1016/j.ejca.2011.06.041

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Medulloblastoma (MB), the most common malignant brain tumour in children, is characterised by a high risk of leptomeningeal dissemination. But little is known about the molecular mechanisms that promote cancer cell migration in MB. Aberrant expression of miR-21 is recognised to be causatively linked to metastasis in a variety of human neoplasms including brain tumours; however its function in MB is still unknown. In this study we investigated the expression level and the role of miR-21 in MB cell migration. miR-21 was found to be up-regulated, compared to normal cerebellum, in 29/29 MB primary samples and 6/6 MB-derived cell lines. Inverse correlation was observed between miR-21 expression and the metastasis suppressor PDCD4, while miR-21 repression increased the release of PDCD4 protein, suggesting negative regulation of PDCD4 by miR-21 in MB cells. Anti-miR-21 decreased protein expression of the tumour cell invasion mediators MAP4K1 and JNK, which are also known to be negatively regulated by PDCD4, and down-regulated integrin protein that is essential for MB leptomeningeal dissemination. Moreover miR-21 knockdown in MB cells increased the expression of two eminent negative modulators of cancer cell migration, E-Cadherin and TIMP2 proteins that are known to be positively regulated by PDCD4. Finally and importantly, suppression of miR-21 decreased the motility of MB cells and reduced their migration across basement membranes in vitro. Together, these compelling data propose miR-21 pathway as a novel mechanism impacting MB cell dissemination and raises the possibility that curability of selected MB may be improved by pharmaceutical strategies directed towards microRNA-21.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Hämatologie / Onkologie (Pädiatrie)
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine

UniBE Contributor:

D'Ambrosio, Rocco and Arcaro, Alexandre

ISSN:

0959-8049

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:24

Last Modified:

17 Mar 2015 21:04

Publisher DOI:

10.1016/j.ejca.2011.06.041

PubMed ID:

21775132

Web of Science ID:

000297452000014

URI:

https://boris.unibe.ch/id/eprint/8325 (FactScience: 213846)

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