Molecular study of hnRNP K and SET proteins on transcription and translational proteins associated in oral tumorigenesis

• Grant number: 09/10783-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2009
• End date: September 30, 2012
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Andréia Machado Leopoldino
• Grantee: Luciana Oliveira de Almeida
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 06/06334-4 - Study molecular and functional of oncoprotein SET, AP.JP

Abstract

Oral cavity tumors belong to the group of head and neck neoplasias and they are related to the types of epidermoid carcinoma. There is a high incidence in the Brazilian population associated with a poor survival due to a late diagnosis and a high recidive of these tumors, without considering the resistance to the treatment. The identification of molecular markers for diagnosis and prognosis is important for the improvement in the life of patients as well as in the guidance of the treatment. However, it is essential the choice for new candidates to therapeutic targets in order to support the development of new anti tumor drugs. Our group has recently validated three differentially proteins accumulated in oral cavity tumors which have potential of application in prognosis. However, the role of these proteins in the oral cavity tumorigenesis remains unknown. The purpose of this post-doctorate work is to evaluate the role of both proteins SET and hnRNPK in the tumor development, seeking to understand their function in the signaling and transcription and translation regulation of genes potentially significant in the process of transformation, differentiation and metastasis. The methodologies chosen are based on cell lineage culture, proteins super expression of interest in human cell, protein analysis through Western blot, real time PCR to identify transcripts with different quantity in cells (normal expression of the protein versus cell super expressing the protein of interest), methylation quantification through real time PCR, protein identification through mass spectrometry and validation through immunoblot using tumor lineage and lineage super expressing or not the protein of interest. The results expected are the identification and validation of genes regulated by the SET and hnRNPK proteins, seeking for an understanding in the role of these proteins in the tumorigenesis studied, aiming for new therapeutic targets in HNSCC. (AU)

Scientific publications

(4)

(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, MAR 6 2015. (09/52228-0, 13/01355-7, 09/10783-7, 10/20384-0, 13/10898-4)

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, FEB 28 2014. (07/02223-6, 09/52228-0, 09/10783-7, 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, APR 18 2017. (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, DEC 2012. (10/20536-4, 09/52228-0, 09/10783-7, 10/20384-0)