NLRC5 mediates cell proliferation, migration, and invasion by regulating the Wnt/β-catenin signalling pathway in clear cell renal cell carcinoma

Cancer Lett. 2019 Mar 1:444:9-19. doi: 10.1016/j.canlet.2018.11.024. Epub 2018 Dec 11.

Abstract

NLRC5, a newly discovered member of the NLR family, has been reported to regulate immune responses and promote cell proliferation, migration, and invasion in hepatocellular carcinoma. However, to date, the potential regulatory roles and molecular mechanisms by which NLRC5 affects the development and progression of clear cell renal cell carcinoma (ccRCC) remain largely unknown. In this study, human clinical data from The Cancer Genome Atlas database revealed that increased NLRC5 expression was associated with advanced stage and poor prognosis in ccRCC patients. Moreover, experimental results showed that NLRC5 is aberrantly overexpressed in human ccRCC tissues and cell lines. Depletion of NLRC5 attenuated ccRCC cell proliferation, migration, and invasion and suppressed ccRCC growth in a nude mouse model. By contrast, overexpression of NLRC5 promoted the proliferation, migration, and invasion of ccRCC cells in vitro. Additionally, NLRC5 expression is not only positively correlated with β-catenin but also coordinates the activation of the downstream Wnt/β-catenin signalling pathway. Together, our data suggest that NLRC5 may be a potential therapeutic target for ccRCC therapy.

Keywords: NLRC5; Wnt/β-catenin pathway; ccRCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology*
  • Cell Movement*
  • Cell Proliferation*
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness
  • Prognosis
  • Tumor Cells, Cultured
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • Xenograft Model Antitumor Assays
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • Biomarkers, Tumor
  • CTNNB1 protein, human
  • Intracellular Signaling Peptides and Proteins
  • NLRC5 protein, human
  • Wnt Proteins
  • beta Catenin