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

PloS One
Sujitha DuggimpudiJessica I Hoell

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.

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Citations

Nov 25, 2017·Frontiers in Neuroanatomy·Tatiana Popovitchenko, Mladen-Roko Rasin
Feb 9, 2018·Cell Division·Steven BoeynaemsLudo Van Den Bosch
Feb 7, 2019·Frontiers in Genetics·Zoe Butti, Shunmoogum A Patten
Mar 26, 2019·Cancer Biomarkers : Section a of Disease Markers·Aishwarya LaxmiJeena Gupta
Jun 25, 2016·Cell Cycle·Yi-Long WangXiao-Ming Yang
Oct 19, 2017·International Journal of Cancer. Journal International Du Cancer·Aniello CerratoAngela Celetti

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Methods Mentioned

BETA
transgenic
PAR-CLIP
transfection
Immuno-Precipitation
PCR
Flow cytometry

Software Mentioned

DAVID
CLIP
Mock
PAR

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