Oncotarget

Research Papers:

MicroRNA-193b-3p represses neuroblastoma cell growth via downregulation of Cyclin D1, MCL-1 and MYCN

Sarah Andrea Roth, Øyvind H. Hald, Steffen Fuchs, Cecilie Løkke, Ingvild Mikkola, Trond Flægstad, Johannes Schulte and Christer Einvik _

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Oncotarget. 2018; 9:18160-18179. https://doi.org/10.18632/oncotarget.24793

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Abstract

Sarah Andrea Roth1, Øyvind H. Hald2, Steffen Fuchs4,5, Cecilie Løkke1, Ingvild Mikkola3, Trond Flægstad1,2, Johannes Schulte4 and Christer Einvik1,2

1Pediatric Research Group, Department of Clinical Medicine, Faculty of Health Science, The Arctic University of Norway – UiT, Tromsø NO-9037, Norway

2Department of Pediatrics, Division of Child and Adolescent Health, UNN – University Hospital of North-Norway, Tromsø NO-9038, Norway

3Research Group of Pharmacology, Department of Pharmacy, The Arctic University of Norway – UiT, Tromsø NO-9037, Norway

4Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Pediatric Oncology and Hematology/Bone Marrow Transplantation, Berlin 10117, Germany

5Berlin Institute of Health (BIH), Berlin 10178, Germany

Correspondence to:

Christer Einvik, email: [email protected]

Keywords: neuroblastoma; miRNA; tumor suppressor; mir-193b

Received: October 26, 2016     Accepted: February 28, 2018     Published: April 06, 2018

ABSTRACT

Neuroblastoma is the most common diagnosed tumor in infants and the second most common extracranial tumor of childhood. The survival rate of patients with high-risk neuroblastoma is still very low despite intensive multimodal treatments. Therefore, new treatment strategies are needed. In recent years, miRNA-based anticancer therapy has received growing attention. Advances in this novel treatment strategy strongly depends on the identification of candidate miRNAs with broad-spectrum antitumor activity. Here, we identify miR-193b as a miRNA with tumor suppressive properties. We show that miR-193b is expressed at low levels in neuroblastoma cell lines and primary tumor samples. Introduction of miR-193b mimics into nine neuroblastoma cell lines with distinct genetic characteristics significantly reduces cell growth in vitro independent of risk factors such as p53 functionality or MYCN amplification. Functionally, miR-193b induces a G1 cell cycle arrest and cell death in neuroblastoma cell lines by reducing the expression of MYCN, Cyclin D1 and MCL-1, three important oncogenes in neuroblastoma of which inhibition has shown promising results in preclinical testing. Therefore, we suggest that miR-193b may represent a new candidate for miRNA-based anticancer therapy in neuroblastoma.


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