TNIP1-mediated TNF-α/NF-κB signalling cascade sustains glioma cell proliferation

J Cell Mol Med. 2020 Jan;24(1):530-538. doi: 10.1111/jcmm.14760. Epub 2019 Nov 5.

Abstract

As a malignant tumour of the central nervous system, glioma exhibits high incidence and poor prognosis. Although TNIP1 and the TNF-α/NF-κB axis play key roles in immune diseases and inflammatory responses, their relationship and role in glioma remain unknown. Here, we revealed high levels of TNIP1 and TNF-α/NF-κB in glioma tissue. Glioma cell proliferation was activated with TNF-α treatment and showed extreme sensitivity to the TNF receptor antagonist. Furthermore, loss of TNIP1 disbanded the A20 complex responsible for IκB degradation and NF-κB nucleus translocation, and consequently erased TNFα-induced glioma cell proliferation. Thus, our investigation uncovered a vital function of the TNIP1-mediated TNF-α/NF-κB axis in glioma cell proliferation and provides novel insight into glioma pathology and diagnosis.

Keywords: Gliomas; NF-κB; TNF-α; TNIP1; cellular signalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology*
  • Cell Proliferation / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Down-Regulation / genetics
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics
  • Glioma / metabolism*
  • Glioma / pathology*
  • Humans
  • Male
  • Mice, Nude
  • Models, Biological
  • NF-kappa B / metabolism*
  • Signal Transduction*
  • Survival Analysis
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • DNA-Binding Proteins
  • NF-kappa B
  • TNIP1 protein, human
  • Tumor Necrosis Factor-alpha