Journal
EXPERIMENTAL NEUROLOGY
Volume 331, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2020.113380
Keywords
TTDA; p53; Apoptosis; Glioma
Categories
Funding
- National Natural Science Foundation of China [81871701, 81772244]
- Natural Science Fund of Guangdong [2017A030313535, 2017A030313532, 2018A030313533, 2019A1515010178]
- Science and Technology Program of Guangzhou [201707010034, 201707010156]
- President Foundation of Nanfang Hospital, Southern Medical University [2017C044]
- Medical Scientific Research Foundation of Guangdong Province of China [A2019282, A2020108]
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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.
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