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

// Sarah Andrea Roth 1 , Oyvind H. Hald 2 , Steffen Fuchs 4, 5 , Cecilie Lokke 1 , Ingvild Mikkola 3 , Trond Flaegstad 1, 2 , Johannes Schulte 4 and Christer Einvik 1, 2 1 Pediatric Research Group, Department of Clinical Medicine, Faculty of Health Science, The Arctic University of Norway – UiT, Tromso NO-9037, Norway 2 Department of Pediatrics, Division of Child and Adolescent Health, UNN – University Hospital of North-Norway, Tromso NO-9038, Norway 3 Research Group of Pharmacology, Department of Pharmacy, The Arctic University of Norway – UiT, Tromso NO-9037, Norway 4 Charite – Universitatsmedizin Berlin, Corporate Member of Freie Universitat Berlin, Humboldt-Universitat zu Berlin, and Berlin Institute of Health, Department of Pediatric Oncology and Hematology/Bone Marrow Transplantation, Berlin 10117, Germany 5 Berlin Institute of Health (BIH), Berlin 10178, Germany Correspondence to: Christer Einvik, email: christer.einvik@uit.no 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.