DUSP2 affects bladder cancer prognosis by down-regulating MEK/ERK and P38 MAPK signaling pathways through PTPN7

Cell Signal. 2023 Dec:112:110893. doi: 10.1016/j.cellsig.2023.110893. Epub 2023 Sep 20.

Abstract

Background: As one of the leading causes of cancer death worldwide, bladder cancer (BCa) ranks 12th in incidence rate. Dual Specific Phosphatase 2 (DUSP2) is a member of the bispecific protein phosphatase subfamily. DUSP2 is closely related to the prognosis of cancer, but the role of DUSP2 in bladder cancer is still unclear. This study aims to explore how DUSP2 affects the prognosis of bladder cancer and clarify the important mechanism in bladder cancer.

Methods: Bioinformatics and experiments have detected the anti-tumor effect of DUSP2. Construct a DUSP2 overexpression cell model, and then use protein blotting experiments to verify the efficiency of transfection. The effects of DUSP2 on proliferation, metastasis, apoptosis, epithelial mesenchymal transition (EMT) and immune invasion of bladder cancer cells were detected in vitro or in vivo. In addition, the mechanism of DUSP2 regulating MEK/ERK through PTPN7 pathway and P38 MAPK inhibiting the progression of bladder cancer was also discussed.

Results: The expression of DUSP2 was down regulated in bladder cancer samples and cell lines. The overexpression of DUSP2 inhibits the proliferation, metastasis and immune microenvironment of bladder cancer cells. In addition, we confirmed that DUSP2 regulates MEK/ERK and P38 MAPK through PTPN7 pathway to inhibit the progression of bladder cancer.

Conclusion: DUSP2 inhibits the progression of bladder cancer by regulating PTPN7. These results suggest that DUSP2/PTPN7/MEK/ERK pathway may become a new therapeutic target for bladder cancer.

Keywords: Bladder cancer; DUSP2; Immune infiltration; MEK/ERK signaling pathway; PTPN7.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation / genetics
  • Dual Specificity Phosphatase 2 / metabolism
  • Humans
  • MAP Kinase Signaling System*
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Protein Tyrosine Phosphatases, Non-Receptor
  • Tumor Microenvironment
  • Urinary Bladder / metabolism
  • Urinary Bladder Neoplasms* / genetics
  • Urinary Bladder Neoplasms* / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • p38 Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase Kinases
  • PTPN7 protein, human
  • Protein Tyrosine Phosphatases, Non-Receptor
  • DUSP2 protein, human
  • Dual Specificity Phosphatase 2