细胞周期调节因子CCDC6是RNA结合蛋白EWS的关键靶点。
The cell cycle regulator CCDC6 is a key target of RNA-binding protein EWS.
作者信息
Duggimpudi Sujitha, Larsson Erik, Nabhani Schafiq, Borkhardt Arndt, Hoell Jessica I
机构信息
Department of Pediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
Department of Medical Biochemistry and Cell biology, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Sweden.
出版信息
PLoS One. 2015 Mar 9;10(3):e0119066. doi: 10.1371/journal.pone.0119066. eCollection 2015.
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.
EWSR1基因易位至ETS转录因子编码区被认为是尤因肉瘤的主要病因。以往的研究集中在这种易位导致的嵌合转录因子的生物学特性上。然而，这些肿瘤中EWSR1杂合缺失的生理后果在很大程度上仍不清楚。此前，我们利用PAR-CLIP鉴定了与EWS结合的各种mRNA。在本研究中，我们证明了已知的细胞周期调节蛋白CCDC6是受EWS调控的新靶点。siRNA介导的EWS下调以CCDC6依赖的方式导致细胞凋亡增加。重新表达CCDC6后，这种效应得以挽救。本研究为野生型EWS在尤因肉瘤中以靶点依赖的方式发挥作用提供了新的功能联系证据。
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