DUSP3 restrains the progression and stemness property of osteosarcoma through regulating EGFR/STAT3/SOX2 axis

Int J Biol Sci. 2025 Jan 1;21(1):160-174. doi: 10.7150/ijbs.101137. eCollection 2025.

Abstract

Background: Dual-specificity phosphatase 3 (DUSP3) is a small-molecule dual-specificity phosphatase whose function has not yet been elucidated. This study investigated the effects of DUSP3 on the biological behavior of osteosarcoma and its potential mechanisms. Methods: We performed bioinformatics analysis of DUSP3 using "The Cancer Genome Atlas" and "The Tumor Immune Estimation Resource" databases. The impact of DUSP3 on osteosarcoma biological behavior was evaluated using CCK-8, wound-healing, transwell invasion, and tumor sphere formation assays. Immunoprecipitation assays confirmed the interaction between two proteins. We then established a nude mouse transplantation tumor model to examine the in vivo effects of DUSP3 on osteosarcoma. Results: Overexpression of DUSP3 significantly inhibited osteosarcoma cell proliferation, migration, invasion, and stemness. Conversely, DUSP3 knockdown yielded the opposite results. In an animal model, we administered subcutaneous injections of 143B osteosarcoma cells overexpressing DUSP3, and the results indicated that the overexpression of DUSP3 impaired osteosarcoma growth. Conclusion: Our findings indicate that DUSP3 could be an independent prognostic determinant in individuals diagnosed with osteosarcoma. Through modulating the EGFR/STAT3/SOX2 axis, DUSP3 restrains osteosarcoma cell growth, migration, invasion, and stemness. Therefore, targeting DUSP3 may serve as an effective therapeutic target in osteosarcoma treatment.

Keywords: DUSP3; osteosarcoma; proliferation; stemness; therapeutic.

MeSH terms

  • Animals
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Dual Specificity Phosphatase 3* / genetics
  • Dual Specificity Phosphatase 3* / metabolism
  • ErbB Receptors* / genetics
  • ErbB Receptors* / metabolism
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude*
  • Osteosarcoma* / genetics
  • Osteosarcoma* / metabolism
  • Osteosarcoma* / pathology
  • SOXB1 Transcription Factors* / genetics
  • SOXB1 Transcription Factors* / metabolism
  • STAT3 Transcription Factor* / metabolism

Substances

  • STAT3 Transcription Factor
  • ErbB Receptors
  • SOXB1 Transcription Factors
  • Dual Specificity Phosphatase 3
  • STAT3 protein, human
  • EGFR protein, human
  • SOX2 protein, human
  • DUSP3 protein, human