Daniel Senfter1, Erdogan Pekcan Erkan1, Erdener Özer2, Gerhard Jungwirth1, Sibylle Madlener1, Marcel Kool3, Thomas Ströbel4, Nurten Saydam1,5, Okay Saydam1,5. 1. Department of Pediatrics and Adolescent Medicine, Molecular Neuro-oncology Research Unit, Medical University of Vienna, Vienna, Austria. 2. Department of Pathology, School of Medicine, Dokuz Eylül University, Izmir, Turkey. 3. Division of Pediatric Neuro-Oncology, German Cancer Research Center DKFZ, Germany. 4. Institute of Neurology, Medical University of Vienna, Vienna, Austria. 5. Department of Neurology, Neurogenetics Unit, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts.
Abstract
BACKGROUND: Overexpression of minichromosome maintenance (MCM) proteins 2, 3, and 7 is associated with migration and invasion in medulloblastoma (MB). However, expression profiling of all prereplication complex (pre-RC) has not been addressed in MBs. PROCEDURE: We performed mRNA expression profiling of a large set of pre-RC elements in cell lines and tumor tissues of MB. RNAi technology was employed for functional studies in MB cell lines. RESULTS: Our data showed that most of the pre-RC components are significantly overexpressed in MB. Among all pre-RC mRNAs, MCM10 showed the highest level of expression (∼500- to 1,000-fold) in MB cell lines and tissues compared to the levels detected in cerebellum. In addition, RNAi silencing of MCM10 caused reduced cell proliferation and cell viability in MB cells. CONCLUSIONS: Taken together, our study reveals that the pre-RC is dysregulated in MB. In addition, MCM10, a member of this complex, is significantly overexpressed in MB and is required for tumor cell proliferation.
BACKGROUND: Overexpression of minichromosome maintenance (MCM) proteins 2, 3, and 7 is associated with migration and invasion in medulloblastoma (MB). However, expression profiling of all prereplication complex (pre-RC) has not been addressed in MBs. PROCEDURE: We performed mRNA expression profiling of a large set of pre-RC elements in cell lines and tumor tissues of MB. RNAi technology was employed for functional studies in MB cell lines. RESULTS: Our data showed that most of the pre-RC components are significantly overexpressed in MB. Among all pre-RC mRNAs, MCM10 showed the highest level of expression (∼500- to 1,000-fold) in MB cell lines and tissues compared to the levels detected in cerebellum. In addition, RNAi silencing of MCM10 caused reduced cell proliferation and cell viability in MB cells. CONCLUSIONS: Taken together, our study reveals that the pre-RC is dysregulated in MB. In addition, MCM10, a member of this complex, is significantly overexpressed in MB and is required for tumor cell proliferation.
Authors: Carolyn N Paulson; Kristen John; Ryan M Baxley; Fredy Kurniawan; Kayo Orellana; Rawle Francis; Alexandra Sobeck; Brandt F Eichman; Walter J Chazin; Hideki Aihara; Gunda I Georg; Jon E Hawkinson; Anja-Katrin Bielinsky Journal: Open Biol Date: 2019-08-14 Impact factor: 6.411