EDARADD silencing suppresses the proliferation and migration of bladder cancer cells

Urol Oncol. 2022 Aug;40(8):382.e15-382.e24. doi: 10.1016/j.urolonc.2022.04.017. Epub 2022 May 28.

Abstract

Purpose: Bladder cancer is a kind of common malignant cancer in the urinary system. The expression of EDARADD (ectodysplasin-A receptor-associated death domain) in bladder cancer is higher than the normal samples. However, its role in bladder cancer remains unknown. In the present study, we analyzed the expression of EDARADD in 81 bladder cancer samples by immunohistochemistry as well as its correlation with clinical characteristics. In addition, the role of EDARADD was also explored through loss of function.

Materials and methods: Cell proliferation assay and MTT assay were conducted to assess the proliferation of bladder cancer cells and transwell assay and wound healing assay were conducted to assess the migration of bladder cancer cells. On the other hand, the levels of epithelial-mesenchymal transition (EMT) associated proteins and the key molecules in the MAPK signaling pathway were detected by western blot. In vivo experiments were also conducted to determine the effect of EDARADD silencing on the metastasis of bladder cancer cells and the MAPK signaling pathway.

Results: EDARADD was highly expressed in bladder cancer samples, especially in high-grade bladder cancer samples. The high EDARADD level indicated a poor survival. Interestingly, EDARADD silencing suppressed the proliferation, migration and EMT of bladder cancer cells. Furthermore, the MAPK signaling pathway was repressed by EDARADD silencing. Additionally, silencing EDARADD also inhibited the metastasis of bladder cancer and the MAPK signaling pathway in vivo. It is indicated that silencing EDARADD may suppress the proliferation and metastasis of bladder cancer cells through the MAPK signaling pathway.

Conclusion: These results indicate that EDARADD may become a probable target for the treatment of bladder cancer.

Keywords: Bladder cancer; EDARADD; MAPK; metastasis; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Edar-Associated Death Domain Protein / metabolism
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Invasiveness / genetics
  • Urinary Bladder Neoplasms* / pathology

Substances

  • EDARADD protein, human
  • Edar-Associated Death Domain Protein