The cell cycle regulator CCDC6 is a key target of RNA-binding protein EWS

Sujitha Duggimpudi; Erik Larsson; Schafiq Nabhani; Arndt Borkhardt; Jessica I Hoell

doi:10.1371/journal.pone.0119066

The cell cycle regulator CCDC6 is a key target of RNA-binding protein EWS

PLoS One. 2015 Mar 9;10(3):e0119066. doi: 10.1371/journal.pone.0119066. eCollection 2015.

Authors

Sujitha Duggimpudi¹, Erik Larsson², Schafiq Nabhani¹, Arndt Borkhardt¹, Jessica I Hoell¹

Affiliations

¹ Department of Pediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
² Department of Medical Biochemistry and Cell biology, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Sweden.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3' Untranslated Regions
Apoptosis
Bone Neoplasms / genetics*
Bone Neoplasms / metabolism
Calmodulin-Binding Proteins / genetics
Calmodulin-Binding Proteins / metabolism*
Cell Line, Tumor
Cell Proliferation
Cytoskeletal Proteins / genetics*
Cytoskeletal Proteins / metabolism
Down-Regulation
Gene Knockdown Techniques
Humans
RNA, Messenger / metabolism
RNA-Binding Protein EWS
RNA-Binding Proteins / genetics
RNA-Binding Proteins / metabolism*
Sarcoma, Ewing / genetics*
Sarcoma, Ewing / metabolism

Substances

3' Untranslated Regions
CCDC6 protein, human
Calmodulin-Binding Proteins
Cytoskeletal Proteins
EWSR1 protein, human
RNA, Messenger
RNA-Binding Protein EWS
RNA-Binding Proteins

Grants and funding

This work was supported by a “Forschungsstipendium der Vereinigung rheinisch-westfälischer Kinder- und Jugendärzte und Kinderchirurgen” fellowship and Elterninitiative Kinderkrebsklinik e.V. Düsseldorf. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.