Potential protective role of Grainyhead-like genes in the development of clear cell renal cell carcinoma

Mol Carcinog. 2017 Nov;56(11):2414-2423. doi: 10.1002/mc.22682. Epub 2017 Jun 15.

Abstract

The involvement of Grainyhead-like (GRHL) transcription factors in various cancers is well documented. However, little is known about their role in clear cell renal cell carcinoma (ccRCC). We discovered that the expression of two of these factors-GRHL1 and GRHL2-are downregulated in ccRCC samples, and their expression is correlated with the expression of VHL gene. This suggests a functional link between the GRHL transcription factors and one of the best known tumor suppressors. Although the GRHL genes are not mutated in ccRCC, some of the single nucleotide polymorphisms in these genes may indicate an increased risk of ccRCC development and/or may allow to assess patients' prognoses and predict their responses to various forms of therapy. Silencing of GRHL2 expression in non-tumorigenic kidney cell line results in increased cell proliferation, increased resistance to apoptosis, as well as changes in the levels of selected proteins involved in the pathogenesis of ccRCC. These changes support the potential role for GRHL2 as a suppressor of ccRCC.

Keywords: gene expression; genes, tumor suppressor; kidney neoplasms; polymorphism, single nucleotide; transcription factors.

MeSH terms

  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing
  • Humans
  • Kidney / metabolism
  • Kidney / pathology*
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • Male
  • Polymorphism, Single Nucleotide
  • Repressor Proteins / genetics
  • Transcription Factors / genetics*

Substances

  • DNA-Binding Proteins
  • GRHL1 protein, human
  • GRHL2 protein, human
  • GRHL3 protein, human
  • Repressor Proteins
  • Transcription Factors