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The DEAD/DEAH Box Helicase, DDX11, Is Essential for the Survival of Advanced Clear Cell Renal Cell Carcinoma and Is a Determinant of PARP Inhibitor Sensitivity

Authors
 Jee Soo Park  ;  Myung Eun Lee  ;  Won Sik Jang  ;  Koon Ho Rha  ;  Seung Hwan Lee  ;  Jongsoo Lee  ;  Won Sik Ham 
Citation
 CANCERS, Vol.13(11) : 2574, 2021-05 
Journal Title
CANCERS
Issue Date
2021-05
Keywords
786-O ; DDX11 ; PARP inhibitor ; olaparib ; renal cell carcinoma ; sunitinib
Abstract
Genes associated with the DEAD-box helicase DDX11 are significant biomarkers of aggressive renal cell carcinoma (RCC), but their molecular function is poorly understood. We analyzed the molecular pathways through which DDX11 is involved in RCC cell survival and poly (ADP-ribose) polymerase (PARP) inhibitor sensitivity. Immunohistochemistry and immunoblotting determined DDX11 expression in normal kidney tissues, benign renal tumors, and RCC tissues and cell lines. Quantitative polymerase chain reaction validated the downregulation of DDX11 in response to transfection with DDX11-specific small interfering RNA. Proliferation analysis and apoptosis assays were performed to determine the impact of DDX11 knockdown on RCC cells, and the relevant effects of sunitinib, olaparib, and sunitinib plus olaparib were evaluated. DDX11 was upregulated in high-grade, advanced RCC compared to low-grade, localized RCC, and DDX11 was not expressed in normal kidney tissues or benign renal tumors. DDX11 knockdown resulted in the inhibition of RCC cell proliferation, segregation defects, and rapid apoptosis. DDX11-deficient RCC cells exhibited significantly increased sensitivity to olaparib compared to sunitinib alone or sunitinib plus olaparib combination treatments. Moreover, DDX11 could determine PARP inhibitor sensitivity in RCC. DDX11 could serve as a novel therapeutic biomarker for RCC patients who are refractory to conventional targeted therapies and immunotherapies.
Files in This Item:
T202101925.pdf Download
DOI
10.3390/cancers13112574
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Urology (비뇨의학교실) > 1. Journal Papers
Yonsei Authors
Rha, Koon Ho(나군호) ORCID logo https://orcid.org/0000-0001-8588-7584
Park, Jee Soo(박지수) ORCID logo https://orcid.org/0000-0001-9976-6599
Lee, Seung Hwan(이승환) ORCID logo https://orcid.org/0000-0001-7358-8544
Lee, Jong Soo(이종수) ORCID logo https://orcid.org/0000-0002-9984-1138
Jang, Won Sik(장원식) ORCID logo https://orcid.org/0000-0002-9082-0381
Ham, Won Sik(함원식) ORCID logo https://orcid.org/0000-0003-2246-8838
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/184044
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