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

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2021 Jun 2

PMID 34073906

Citations 6

Authors

Jee Soo Park

Myung Eun Lee

Won Sik Jang

Koon Ho Rha

Seung Hwan Lee

Jongsoo Lee

Won Sik Ham

Affiliations

Soon will be listed here.

Abstract

Genes associated with the DEAD-box helicase 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 -specific small interfering RNA. Proliferation analysis and apoptosis assays were performed to determine the impact of 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. knockdown resulted in the inhibition of RCC cell proliferation, segregation defects, and rapid apoptosis. -deficient RCC cells exhibited significantly increased sensitivity to olaparib compared to sunitinib alone or sunitinib plus olaparib combination treatments. Moreover, could determine PARP inhibitor sensitivity in RCC. could serve as a novel therapeutic biomarker for RCC patients who are refractory to conventional targeted therapies and immunotherapies.

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