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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

Grant number: 10/20384-0
Support Opportunities:Regular Research Grants
Duration: May 01, 2011 - April 30, 2013
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Andréia Machado Leopoldino
Grantee:Andréia Machado Leopoldino
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated researchers:Carlos Curti ; J. Silvio Gutkind ; Lewis Joel Greene


As one of the subtypes of head and neck cancer (PBC), the oral squamous cell carcinoma, is the head and neck cancer more common and is strongly associated with use of tobacco and alcohol. The multifunctional protein SET is an oncoprotein involved in the regulation of apoptosis, transcription, besides being a subunit complex that inhibits histone acetylation by binding to and masking histone acetyltransferase targets of keeping the target DNA in its form hipoacetylated and, therefore contributing to the maintenance of DNA and genes silenced. However, potential targets of SET, regulatory RNAs (miRNAs) and processes such as apoptosis and cell migration have not been thoroughly checked. Our goal is to obtain quantitative and qualitative information regarding the expression of RNAs, miRNAs and proteins using model in vitro and in vivo (xenograft and transgenic animal for SET) regulated by SET protein in normal and tumor cells. (AU)

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Scientific publications (7)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ALMEIDA, LUCIANA O.; GOTO, RENATA N.; NETO, MARINALDO P. C.; SOUSA, LUCAS O.; CURTI, CARLOS; LEOPOLDINO, ANDREIA M.. SET overexpression in HEK293 cells regulates mitochondrial uncoupling proteins levels within a mitochondrial fission/reduced autophagic flux scenario. Biochemical and Biophysical Research Communications, v. 458, n. 2, p. 300-306, . (09/52228-0, 13/01355-7, 09/10783-7, 10/20384-0, 13/10898-4)
LEOPOLDINO, ANDREIA M.; SQUARIZE, CRISTIANE H.; GARCIA, CRISTIANA B.; ALMEIDA, LUCIANA O.; PESTANA, CEZAR R.; SOBRAL, LAYS M.; UYEMURA, SERGIO A.; TAJARA, ELOIZA H.; GUTKIND, J. SILVIO; CURTI, CARLOS. SET protein accumulates in HNSCC and contributes to cell survival: Antioxidant defense, Akt phosphorylation and AVOs acidification. Oral Oncology, v. 48, n. 11, p. 1106-1113, . (05/03380-2, 10/20384-0, 09/52228-0, 06/06334-4)
ALMEIDA, LUCIANA O.; GARCIA, CRISTIANA B.; MATOS-SILVA, FLAVIA A.; CURTI, CARLOS; LEOPOLDINO, ANDREIA M.. Accumulated SET protein up-regulates and interacts with hnRNPK, increasing its binding to nucleic acids, the Bcl-xS repression, and cellular proliferation. Biochemical and Biophysical Research Communications, v. 445, n. 1, p. 196-202, . (07/02223-6, 09/52228-0, 09/10783-7, 10/20384-0, 13/10898-4)
SOBRAL, LAYS M.; SOUSA, LUCAS O.; COLETTA, RICARDO D.; CABRAL, HAMILTON; GREENE, LEWIS J.; TAJARA, ELOIZA H.; GUTKIND, J. SILVIO; CURTI, CARLOS; LEOPOLDINO, ANDREIA M.. Stable SET knockdown in head and neck squamous cell carcinoma promotes cell invasion and the mesenchymal-like phenotype in vitro, as well as necrosis, cisplatin sensitivity and lymph node metastasis in xenograft tumor models. Molecular Cancer, v. 13, . (10/18544-9, 09/52228-0, 13/08135-2, 10/20384-0, 13/10898-4)
ALMEIDA, LUCIANA O.; NETO, MARINALDO P. C.; SOUSA, LUCAS O.; TANNOUS, MARYNA A.; CURTI, CARLOS; LEOPOLDINO, ANDREIA M.. SET oncoprotein accumulation regulates transcription through DNA demethylation and histone hypoacetylation. ONCOTARGET, v. 8, n. 16, p. 26802-26818, . (13/10898-4, 10/20536-4, 13/08135-2, 10/20384-0, 09/52228-0, 09/10783-7)
ALMEIDA, LUCIANA O.; GOTO, RENATA N.; PESTANA, CEZAR R.; UYEMURA, SERGIO A.; GUTKIND, SILVIO; CURTI, CARLOS; LEOPOLDINO, ANDREIA M.. SET overexpression decreases cell detoxification efficiency: ALDH2 and GSTP1 are downregulated, DDR is impaired and DNA damage accumulates. FEBS Journal, v. 279, n. 24, p. 4615-4628, . (10/20536-4, 09/52228-0, 09/10783-7, 10/20384-0)
SOUSA, LUCAS OLIVEIRA; SOBRAL, LAYS MARTIN; DE ALMEIDA, LUCIANA OLIVEIRA; GARCIA, CRISTIANA BERNADELLI; GREENE, LEWIS JOEL; LEOPOLDINO, ANDREIA MACHADO. SET protein modulates H4 histone methylation status and regulates miR-137 level in oral squamous cell carcinoma. Epigenomics, v. 12, n. 6, p. 475-485, . (10/20384-0, 16/19103-2, 13/10898-4, 13/08135-2)

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