CARD10 promotes the progression of renal cell carcinoma by regulating the NF‑κB signaling pathway

Mol Med Rep. 2020 Jan;21(1):329-337. doi: 10.3892/mmr.2019.10840. Epub 2019 Nov 21.

Abstract

Previous studies have demonstrated that the expression of CARD10 is closely associated with the occurrence of tumors, and its role is mainly to promote tumor progression by activating the transcription factor NF‑κB. However, the signaling pathway in renal cancer remains unclear. The objective of the present study was to investigate the ability of caspase recruitment domain 10 (CARD10) to regulate the NF‑κB signaling pathway and promote the progression of renal cell carcinoma (RCC). Expression of CARD10 in ACHN, 786‑O and HK‑2 cells was evaluated via western blot analysis, as was the epidermal growth factor (EGF)‑induced activation of NF‑κB signaling pathway‑related proteins in cells. The expression of CARD10 was inhibited by CARD10 short hairpin RNA transfection. Cell cycle analysis and MTT assays were used to evaluate cell proliferation. Cell apoptosis was analyzed via flow cytometry. The invasion of renal cell lines was detected via Transwell cell migration and invasion assays in vitro. The results showed that CARD10 expression was significantly higher in RCC cells than in normal renal tubular epithelial cells. CARD10 silencing inhibited the proliferation, invasion and migration of RCC cells. EGF stimulation upregulated the activation of the NF‑κB pathway in RCC cells. Inhibition of CARD10 expression inhibited NF‑κB activation in RCC cells. Taken together, these data suggested that CARD10 promotes the progression of renal cell carcinoma by regulating the NF‑κB signaling pathway. Thus, this indicated that CARD10 may be a novel therapeutic target in RCC.

Keywords: proliferation and metastasis; caspase recruitment domain 10; nF-κB signaling pathway; western blot analysis.

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics
  • CARD Signaling Adaptor Proteins / genetics
  • CARD Signaling Adaptor Proteins / metabolism*
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Epidermal Growth Factor / pharmacology
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • NF-kappa B / metabolism*
  • RNA, Small Interfering
  • Signal Transduction / drug effects
  • Signal Transduction / genetics*
  • Up-Regulation

Substances

  • CARD Signaling Adaptor Proteins
  • CARD10 protein, human
  • NF-kappa B
  • RNA, Small Interfering
  • Epidermal Growth Factor