RIP2 promotes glioma cell growth by regulating TRAF3 and activating the NF‑κB and p38 signaling pathways

Oncol Rep. 2018 Jun;39(6):2915-2923. doi: 10.3892/or.2018.6397. Epub 2018 Apr 23.


Receptor‑interacting protein 2 (RIP2) has recently been reported to be involved in tumor infiltration and cancer metastasis. However, the function of RIP2 in human astrocytoma remains unclear. In the present study, we showed that the expressions of RIP2 and Bcl‑xL were positively correlated with the malignant grade in 28 cases of astrocytoma of various grades and 6 cases of normal human tissues. In addition, increased activity of the NF‑κB and p38 signaling pathways in astrocytoma tissue was observed. Cytological experiments indicated that RIP2 promoted human glioblastoma cell proliferation by inducing expression of Bcl‑xL, and knockdown of endogenous RIP2 promoted cell apoptosis. Mechanistically, knockdown of RIP2 suppressed downstream events including the canonical and alternative NF‑κB pathway as well as the mitogen‑activated protein kinase (p38) pathway. In addition, the present study also demonstrated that tumor necrosis factor receptor‑associated factor 3 (TRAF3), as a novel RIP2 binding partner, was downregulated in glioma tissues and functionally was a negative regulator involved in RIP2‑induced glioma cell growth. Taken together, the present study established a negative link between RIP2 and TRAF3 proteins and identifies a new pathway for regulating astrocytoma progression.

MeSH terms

  • Adult
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics
  • Glioma / metabolism
  • Glioma / pathology*
  • Humans
  • MAP Kinase Signaling System
  • Male
  • Middle Aged
  • NF-kappa B / metabolism
  • Neoplasm Grading
  • Receptor-Interacting Protein Serine-Threonine Kinase 2 / genetics*
  • Receptor-Interacting Protein Serine-Threonine Kinase 2 / metabolism
  • TNF Receptor-Associated Factor 3 / genetics*
  • TNF Receptor-Associated Factor 3 / metabolism
  • bcl-X Protein / genetics*
  • bcl-X Protein / metabolism


  • BCL2L1 protein, human
  • NF-kappa B
  • TNF Receptor-Associated Factor 3
  • TRAF3 protein, human
  • bcl-X Protein
  • RIPK2 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinase 2