NCOA7 Regulates Growth and Metastasis of Clear Cell Renal Cell Carcinoma via MAPK/ERK Signaling Pathway

Int J Mol Sci. 2023 Jul 18;24(14):11584. doi: 10.3390/ijms241411584.

Abstract

NCOA7 is a nuclear receptor coactivator that is downregulated in a variety of cancers. However, the expression and prognostic significance of NCOA7 in clear cell renal cell carcinoma (ccRCC) remain unknown. The expression of NCOA7 in ccRCC tissues was analyzed using bioinformatics analysis, Western blotting, and immunohistochemistry. Kaplan-Meier analysis, the receiver operating characteristic (ROC) curve, and clinicopathological correlation analysis were used to assess the predictive power of NCOA7. Overexpression function tests were conducted in cells and mouse models to clarify the function and mechanism of NCOA7 in inhibiting the progression of ccRCC. NCOA7 expression was downregulated in all three subtypes of renal cell carcinoma, and only had significant prognostic value for patients with ccRCC. NCOA7 overexpression inhibited the proliferation, invasion, and metastasis of ccRCC cells in vivo and in vitro. Mechanistically, NCOA7 inhibited the MAPK/ERK pathway to regulate epithelial-mesenchymal transformation (EMT) and apoptosis, thereby inhibiting the progression of ccRCC. NCOA7 inhibits tumor growth and metastasis of ccRCC through the MAPK/ERK pathway, thus indicating its potential as a prognostic marker and therapeutic target for ccRCC.

Keywords: MAPK pathway; NCOA7; clear cell renal cell carcinoma; epithelial–mesenchymal transformation (EMT); molecular target.

MeSH terms

  • Animals
  • Carcinoma
  • Carcinoma, Renal Cell* / genetics
  • Carcinoma, Renal Cell* / metabolism
  • Carcinoma, Renal Cell* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kidney Neoplasms* / genetics
  • Kidney Neoplasms* / metabolism
  • Kidney Neoplasms* / pathology
  • MAP Kinase Signaling System
  • Mice
  • Signal Transduction

Substances

  • NCOA7 protein, human
  • Ncoa7 protein, mouse