Altered RECQL5 expression in urothelial bladder carcinoma increases cellular proliferation and makes RECQL5 helicase activity a novel target for chemotherapy
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Karl Patterson1, Lovleen Arya1,*, Sarah Bottomley1, Susan Morgan2, Angela Cox1, James Catto2, Helen E. Bryant1
1Academic Unit of Molecular Oncology, Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, University of Sheffield, Sheffield S10 2RX, United Kingdom
2Academic Unit of Urology, Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, University of Sheffield, Sheffield S10 2RX, United Kingdom
*Current address: DuPont Knowledge Center, E.I.DuPont India Pvt Ltd., ICICI Knowledge Park, Genome Valley, Hyderabad-500078, Andhra Pradesh, India
Helen E. Bryant, email: email@example.com
Keywords: RECQL5, helicase, bladder cancer, targeted therapy
Received: September 08, 2015 Accepted: September 19, 2016 Published: October 15, 2016
RECQ helicases are a family of enzymes with both over lapping and unique functions. Functional autosomal recessive loss of three members of the family BLM, WRN and RECQL4, results in hereditary human syndromes characterized by cancer predisposition and premature aging, but despite the finding that RECQL5 deficient mice are cancer prone, no such link has been made to human RECQL5. Here we demonstrate that human urothelial carcinoma of the bladder (UCC) has increased expression of RECQL5 compared to normal bladder tissue and that increasing RECQL5 expression can drive proliferation of normal bladder cells and is associated with poor prognosis. Further, by expressing a helicase dead RECQL5 and by depleting bladder cancer cells of RECQL5 we show that inhibition of RECQL5 activity has potential as a new target for treatment of UCC.
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