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The role of set protein in miR-9 methylation profile and DNA repair in human oral squamous cell carcinoma

Grant number: 12/12928-5
Support type:Scholarships in Brazil - Master
Effective date (Start): July 01, 2013
Effective date (End): June 30, 2014
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Andréia Machado Leopoldino
Grantee:Maryna Aguilar Tannous
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Head and neck squamous cell carcinomas (HNSCC) are tumors of oral cavity, pharynx and larynx and are the sixth most common cancer worldwide. The onset and progression of oral squamous cell carcinoma (OSCC) is a process characterized by the acquisition of genetic and epigenetic alterations, and these are not fully understood. The neoplastic cells show global DNA hypomethylation and promoter hypermethylation of specific genes. Studies described the hypomethylation of LINE-1 sequences (retrotransposons) as markers of global genomic hypomethylation in cancers, including HNSCC. Global demethylation leads to changes in expression of oncogenes and chromosomal instability. The genomic instability in cancer is also marked by the presence of microsatellite instability (MSI), related to deficiency in DNA repair. Additionally, studies have been conducted to detect the expression profile of microRNAs in HNSCC, and the methylation profile of miR-9 was recently described as an important biomarker. According to our results, there is an accumulation of the SET protein in OSCC, which promotes increase in cell survival. The SET participates in many cellular processes and high levels are found in other cancers. This context suggests SET could be an important therapeutic target and understanding its actions is required. Our study`s hypothesis is the potential role of SET in the induction and/or maintenance of genome instability and in epigenetics regulation. The objective is to analyze the effect of SET silencing in methylation profile of LINE-1 and miR-9 and in MSI using OSCC in vitro and in vivo. The assays will be based on methylation by quantitative real time PCR (qrt-MSP) and MSI by conventional PCR and electrophoresis. RNA silencing was performed using plasmid containing shRNA against SET mRNA in OSCC cell lineages in vitro (HN12 and Cal27) and in vivo (HN12 xenograft tumors).

Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
TANNOUS, Maryna Aguilar. The role of SET protein in miR-9 methylation profile and DNA repair in human oral squamous cell carcinoma. 2014. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto Ribeirão Preto.

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