The cell cycle regulator CCDC6 is a key target of RNA-binding protein EWS.
Genetic translocation of EWSR1 to ETS transcription factor coding region is considered as primary cause for Ewing sarcoma. Previous studies focused on the biology of chimeric transcription factors formed due to this translocation. However, the physiological consequences of heterozygous EWSR1 loss in these tumors have largely remained elusive. Previously, we have identified various mRNAs bound to EWS using PAR-CLIP. In this study, we demonstrate CCDC6, a known cell cycle regulator protein, as a novel target regulated by EWS. siRNA mediated down regulation of EWS caused an elevated apoptosis in cells in a CCDC6-dependant manner. This effect was rescued upon re-expression of CCDC6. This study provides evidence for a novel functional link through which wild-type EWS operates in a target-dependant manner in Ewing sarcoma.
Department of Pediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
Sujitha
S
Duggimpudi
Department of Medical Biochemistry and Cell biology, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Sweden.
Erik
E
Larsson
Department of Pediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
Schafiq
S
Nabhani
Department of Pediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
Arndt
A
Borkhardt
Department of Pediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
Jessica I
JI
Hoell
D020413:3' Untranslated Regions; D017209:Apoptosis; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012512:Sarcoma, Ewing / Q000235:genetics* / Q000378:metabolism
D020413:3' Untranslated Regions; C088832:CCDC6 protein, human; D002148:Calmodulin-Binding Proteins; D003598:Cytoskeletal Proteins; C500986:EWSR1 protein, human; D012333:RNA, Messenger; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins