TRPM2 facilitates tumor progression of clear cell renal cell carcinoma by relieving Endoplasmic Reticulum Stress

Int J Med Sci. 2023 Jan 1;20(1):57-69. doi: 10.7150/ijms.77944. eCollection 2023.

Abstract

Clear cell renal cell carcinoma (ccRCC) has the highest incidence rate among all pathological types of kidney cancers. Although the role of transient receptor potential (TRP) ion channel TRPM2 has been studied in many cancers, its function in ccRCC is still unexplored. In this study, using the KIRC module of TCGA, we found that TRPM2 was upregulated in ccRCC tissues and was related to poor prognosis. Gene set enrichment analysis (GSEA) showed that TRPM2 was related to epithelial-to-mesenchymal transition (EMT), TCA cycle, fatty acid metabolism, and immune system-related functions. Functional experimental results indicated that TRPM2 could promote ccRCC progression. Furthermore, mechanism analysis showed that knocking out TRPM2 can reverse these phenotypes by increasing endoplasmic reticulum stress and decreasing EMT. We also investigated the potential role of TRPM2 in immune cell infiltration in the tumor microenvironment. Our study indicated that TRPM2 promotes ccRCC progression and may be a novel target for ccRCC therapy.

Keywords: Endoplasmic Reticulum Stress; TRPM2; Tumor progression; ccRCC.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Carcinoma, Renal Cell* / pathology
  • Endoplasmic Reticulum Stress / genetics
  • Humans
  • Kidney Neoplasms* / pathology
  • Prognosis
  • TRPM Cation Channels* / genetics
  • Tumor Microenvironment / genetics

Substances

  • TRPM Cation Channels
  • Biomarkers, Tumor
  • TRPM2 protein, human