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Death-associated protein 3 is overexpressed in human thyroid oncocytic tumours
British Journal of Cancer, 06/19/09
Jacques C et al. - In a study to assess whether human death-associated protein 3 (hDAP3) is overexpressed in human thyroid oncocytic tumours, it was found that ELK1 and estrogen-related receptor alpha (ESRRA) may be considered potential regulators of DAP3 gene expression. DAP3 may participate in mitochondrial maintenance and play a role in the balance between mitochondrial homoeostasis and tumourigenesis.
Methods- A search through publicly available microarray data sets showed 337 genes potentially coregulated with the DAP3 gene.
- Promoter sequences of these 337 genes and 70 out of 85 mitochondrial ribosome genes were analysed in silico with the DAP3 gene promoter sequence.
- Mitochondrial role of DAP3 was also investigated in the thyroid tumours presenting various mitochondrial contents.
- The study revealed 9 transcription factors presenting enriched motifs for these gene promoters, 5 of which are implicated in cellular growth (ELK1, ELK4, RUNX1, HOX11-CTF1, TAL1-ternary complex factor 3) and 4 in mitochondrial biogenesis (nuclear respiratory factor-1 [NRF-1], GABPA, PPARG-RXRA, and estrogen-related receptor alpha [ESRRA]).
- An independent microarray data set showed the overexpression of ELK1, RUNX1, and ESRRA in the thyroid oncocytic tumours.
- Exploring the thyroid tumours, DAP3 mRNA and protein expression is upregulated in tumours presenting a mitochondrial biogenesis compared with the normal tissue.
- ELK1 and ESRRA were also showed upregulated with DAP3.
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