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

Jee Soo Park, Myung Eun Lee, Won Sik Jang, Koon Ho Rha, Seung Hwan Lee, Jongsoo Lee, Won Sik Ham

Research output: Contribution to journalArticlepeer-review

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 immunoblot-ting 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.

Original languageEnglish
Article number2574
JournalCancers
Volume13
Issue number11
DOIs
Publication statusPublished - 2021 Jun 1

Bibliographical note

Funding Information:
Funding: This work was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI17C1095), the National Research Foundation of Korea (NRF), funded by the Korean government (MSIT) (grant number: 2019R1A2C1002863), and the National Cancer Center, Republic of Korea (grant number: NCC‐1810861‐1).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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