Y‑box binding protein 1 acts as a negative regulator of stearoyl CoA desaturase 1 in clear cell renal cell carcinoma

Eric Jeffords, Samuel Freeman, Breanna Cole, Kate Root, Thierry Chekouo, Richard G. Melvin, Lynne Bemis, Glenn E. Simmons

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Y‑box binding protein 1 (YB‑1) is a regulatory protein associated with oncogenesis and poor prognosis in patients with cancer. In the cell, YB‑1 functions as a DNA and RNA binding protein that promotes or suppresses expres‑ sion of target genes. The cancer‑promoting activity of YB‑1 is mediated through its activation of oncogenes and repression of tumor suppressor genes. Lipogenic enzyme stearoyl‑CoA desaturase (SCD1) drives the production of endogenous monounsaturated fatty acids (MUFAs) in cells and protects against toxic buildup of saturated fatty acids. Clear cell renal cell carcinoma (ccRCC) is often characterized by aberrantly high SCD1 expression and cytosolic accumulation of unsatu‑ rated fatty acids. In the present study, a proteomics screen of cells treated with inhibitors of SCD1 supported a potential relationship between YB‑1 and SCD1. It was revealed that the presence of MUFAs led to increased protein synthesis and increased expression of high molecular weight forms of YB‑1 in ccRCC cells, but not in non‑tumorigenic cells. Ectopic expression of YB‑1 led to decreased expression levels of SCD1 protein and mRNA in ccRCC cell lines. Conversely, targeted knockdown of YB‑1 increased SCD1 mRNA abundance. Analysis of ccRCC patient data from The Cancer Proteome Atlas database showed YB‑1 expression was negatively associated with survival, whereas SCD1 was associated with improved survival. These data suggested an antagonistic rela‑ tionship between YB‑1 and SCD1 that may influence survival of patients with ccRCC.

Original languageEnglish (US)
Article number12026
JournalOncology Letters
Volume20
Issue number5
DOIs
StatePublished - Aug 2020

Bibliographical note

Funding Information:
The authors would like to acknowledge the support of Ms. Jara McLaren (Simmons Laboratory, UMN Medical School) for providing an early review of the literature regarding func? tion and localization of YB?1 in the context of cancer; Mrs. Barbara Perslin (Department of Biomedical Sciences, UMN Medical School) for administrative support in the ordering of supplies and reagents; Dr Benjamin Clarke (UMN Medical School) for providing the tissue culture facilities for the work done for this manuscript; Mrs. Shannon RedBrook (Clarke Lab) for technical support regarding use of the Clarke labora? tory tissue culture facility; and Dr Jean Regal (Department of Biomedical Sciences, UMN Medical School) for orchestrating critical staff support to the project. This work was supported by the Whiteside Institute for Clinical Research and by the National Institutes of Health's National Center for Advancing Translational Sciences (grant no. UL1TR002494). The content is solely the respon? sibility of the authors and does not necessarily represent the official views of the National Institutes of Health's National Center for Advancing Translational Sciences.

Funding Information:
This work was supported by the Whiteside Institute for Clinical Research and by the National Institutes of Health's National Center for Advancing Translational Sciences (grant no. UL1TR002494). The content is solely the respon‑ sibility of the authors and does not necessarily represent the official views of the National Institutes of Health's National Center for Advancing Translational Sciences.

Publisher Copyright:
© 2020 Spandidos Publications. All rights reserved.

Keywords

  • Cancer
  • Clear cell renal cell carcinoma
  • Kidney
  • Lipid metabolism
  • Monounsaturated fatty acids
  • Stearoyl‑CoA desaturase
  • The Cancer Genome Atlas
  • Y‑box binding protein 1

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