Rebecca Pötschke1,2, Gerrit Gielen3, Torsten Pietsch3, Christof Kramm4, Jan-Henning Klusmann2, Stefan Hüttelmaier5, Caspar D Kühnöl6. 1. Molecular Cell Biology, Institute of Molecular Medicine, Martin-Luther-University, Halle (Saale), Germany. 2. Department of Pediatric Hematology/Oncology, University Hospital, Halle (Saale), Germany. 3. Institute of Neuropathology, University Hospital, Bonn, Germany. 4. Division of Pediatric Hematology and Oncology, University Medical Center, Göttingen, Germany. 5. Molecular Cell Biology, Institute of Molecular Medicine, Martin-Luther-University, Halle (Saale), Germany. stefan.huettelmaier@medizin.uni-halle.de. 6. Department of Pediatric Hematology/Oncology, University Hospital, Halle (Saale), Germany. caspar.kuehnoel@uk-halle.de.
Abstract
BACKGROUND: Glioblastoma (GBM) is the most aggressive form of glioma in adults and children and is associated with very poor prognosis. Pediatric tumors are biologically distinct from adult GBM and differ in response to current GBM treatment protocols. Regarding pediatric GBM, new drug combinations and the molecular background of chemotherapy effects need to be investigated, in order to increase patient survival outcome. METHODS: The expression of the RNA-binding protein Musashi1 (MSI1) in pediatric glioma samples of different WHO tumor grades was investigated on the protein (immunohistochemistry) and on the RNA level (publicly accessible RNA sequencing dataset). The impact of the chemotherapeutic temozolomide (TMZ) in combination with valproic acid (VPA) was tested in two pediatric glioblastoma-derived cell lines. The supportive effect of MSI1 expression against this treatment was investigated via transient knockdown and protein overexpression. RESULTS: MSI1 expression correlates with pediatric high-grade glioma (HGG). The combination of TMZ with VPA significantly increases the impact of drug treatment on cell viability in vitro. MSI1 was found to promote drug resistance to the combined treatment with TMZ and VPA. CONCLUSION: MSI1 expression is a potential marker for pediatric HGG and increases chemoresistance. Inhibition of MSI1 might lead to an improved patient outcome and therapy response.
BACKGROUND:Glioblastoma (GBM) is the most aggressive form of glioma in adults and children and is associated with very poor prognosis. Pediatric tumors are biologically distinct from adult GBM and differ in response to current GBM treatment protocols. Regarding pediatric GBM, new drug combinations and the molecular background of chemotherapy effects need to be investigated, in order to increase patient survival outcome. METHODS: The expression of the RNA-binding protein Musashi1 (MSI1) in pediatric glioma samples of different WHO tumor grades was investigated on the protein (immunohistochemistry) and on the RNA level (publicly accessible RNA sequencing dataset). The impact of the chemotherapeutic temozolomide (TMZ) in combination with valproic acid (VPA) was tested in two pediatric glioblastoma-derived cell lines. The supportive effect of MSI1 expression against this treatment was investigated via transient knockdown and protein overexpression. RESULTS:MSI1 expression correlates with pediatric high-grade glioma (HGG). The combination of TMZ with VPA significantly increases the impact of drug treatment on cell viability in vitro. MSI1 was found to promote drug resistance to the combined treatment with TMZ and VPA. CONCLUSION:MSI1 expression is a potential marker for pediatric HGG and increases chemoresistance. Inhibition of MSI1 might lead to an improved patient outcome and therapy response.
Authors: Christof M Kramm; Sabine Wagner; Stefan Van Gool; Hansjörg Schmid; Ronald Sträter; Astrid Gnekow; Stefan Rutkowski; Johannes E A Wolff Journal: Anticancer Res Date: 2006 Sep-Oct Impact factor: 2.480
Authors: Sheila K Singh; Ian D Clarke; Mizuhiko Terasaki; Victoria E Bonn; Cynthia Hawkins; Jeremy Squire; Peter B Dirks Journal: Cancer Res Date: 2003-09-15 Impact factor: 12.701
Authors: Rebecca Pötschke; Jacob Haase; Markus Glaß; Sebastian Simmermacher; Claudia Misiak; Luiz O F Penalva; Caspar D Kühnöl; Stefan Hüttelmaier Journal: Cancers (Basel) Date: 2020-12-05 Impact factor: 6.639
Authors: Mirella Baroni; Caihong Yi; Saket Choudhary; Xiufen Lei; Adam Kosti; Denise Grieshober; Mitzli Velasco; Mei Qiao; Suzanne S Burns; Patricia R Araujo; Talia DeLambre; Mi Young Son; Michelina Plateroti; Marco A R Ferreira; Paul Hasty; Luiz O F Penalva Journal: Cancers (Basel) Date: 2021-03-24 Impact factor: 6.639