TTDA inhibited apoptosis by regulating the p53-Bax/Bcl2 axis in glioma

Exp Neurol. 2020 Sep:331:113380. doi: 10.1016/j.expneurol.2020.113380. Epub 2020 Jun 12.

Abstract

The trichothiodystrophy group A protein (TTDA) functions in nucleotide excision repair and basal transcription. TTDA plays a role in cancers and serves as a prognostic and predictive factor in high-grade serous ovarian cancer; however, its role in human glioma remains unknown. Here, we found that TTDA was overexpressed in glioma tissues. In vitro experiments revealed that TTDA overexpression inhibited apoptosis of glioma cells and promoted cell growth, whereas knockdown of TTDA had the opposite effect. Increased TTDA expression significantly decreased the Bax/Bcl2 ratio and the level of cleaved-caspase3. TTDA interacted with the p53 gene at the -1959 bp and -1530 bp region and regulated its transcription, leading to inhibition of the p53-Bax/Bcl2 mitochondrial apoptosis pathway in glioma cells. These results indicate that TTDA is an upstream regulator of p53-mediated apoptosis and acts as an oncogene, suggesting its value as a potential molecular target for the diagnosis and treatment of glioma.

Keywords: Apoptosis; Glioma; TTDA; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology*
  • Brain Neoplasms / pathology*
  • Cell Proliferation / physiology
  • Gene Expression Regulation, Neoplastic / physiology*
  • Glioma / pathology*
  • Humans
  • Oncogenes
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction / physiology
  • Transcription Factors / metabolism*
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • BCL2 protein, human
  • GTF2H5 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • TP53 protein, human
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein