| Full text | |
| Author(s): |
Almeida, Luciana O.
;
Neto, Marinaldo P. C.
;
Sousa, Lucas O.
;
Tannous, Maryna A.
;
Curti, Carlos
;
Leopoldino, Andreia M.
Total Authors: 6
|
| Document type: | Journal article |
| Source: | ONCOTARGET; v. 8, n. 16, p. 26802-26818, APR 18 2017. |
| Web of Science Citations: | 6 |
| Abstract | |
Epigenetic modifications are essential in the control of normal cellular processes and cancer development. DNA methylation and histone acetylation are major epigenetic modifications involved in gene transcription and abnormal events driving the oncogenic process. SET protein accumulates in many cancer types, including head and neck squamous cell carcinoma (HNSCC); SET is a member of the INHAT complex that inhibits gene transcription associating with histones and preventing their acetylation. We explored how SET protein accumulation impacts on the regulation of gene expression, focusing on DNA methylation and histone acetylation. DNA methylation profile of 24 tumour suppressors evidenced that SET accumulation decreased DNA methylation in association with loss of 5-methylcytidine, formation of 5-hydroxymethylcytosine and increased TET1 levels, indicating an active DNA demethylation mechanism. However, the expression of some suppressor genes was lowered in cells with high SET levels, suggesting that loss of methylation is not the main mechanism modulating gene expression. SET accumulation also downregulated the expression of 32 genes of a panel of 84 transcription factors, and SET directly interacted with chromatin at the promoter of the downregulated genes, decreasing histone acetylation. Gene expression analysis after cell treatment with 5-aza-2'-deoxycytidine (5-AZA) and Trichostatin A (TSA) revealed that histone acetylation reversed transcription repression promoted by SET. These results suggest a new function for SET in the regulation of chromatin dynamics. In addition, TSA diminished both SET protein levels and SET capability to bind to gene promoter, suggesting that administration of epigenetic modifier agents could be efficient to reverse SET phenotype in cancer (AU) | |
| FAPESP's process: | 13/10898-4 - Study of the molecular mechanisms by protein SET with impact on tumorigenesis and progression of oral cancer |
| Grantee: | Carlos Curti |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 10/20536-4 - Study of functions of the acidic domain and NAP domain of SET protein in cell line |
| Grantee: | Renata Nishida Goto |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |
| FAPESP's process: | 13/08135-2 - CTC - Center for Cell-Based Therapy |
| Grantee: | Dimas Tadeu Covas |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 10/20384-0 - Identification of genes, miRNAs and proteins regulated by set oncoprotein and associated on malignization and tumor progression in HNSCC using in vitro and in vivo models |
| Grantee: | Andréia Machado Leopoldino |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 09/52228-0 - Studies on resistance to apoptosis in cancer, head/neck model: signaling via with emphasis on PIP3-Akt/SET, oxidative stress, mitochondria and relationships |
| Grantee: | Carlos Curti |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 09/10783-7 - Molecular study of hnRNP K and SET proteins on transcription and translational proteins associated in oral tumorigenesis |
| Grantee: | Luciana Oliveira de Almeida |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |