Investigation of epigenetic mechanisms regulated by HIF1A and their target transcripts on medulloblastoma cell line after hypoxia exposition

• Grant number: 12/06592-4
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: January 16, 2013
• End date: May 15, 2013
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Elvis Terci Valera
• Grantee: Gustavo Alencastro Veiga Cruzeiro
• Supervisor: Agda Karina Brodoloni Eterovic
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Texas Health Science Center at Houston (UTHealth), United States
• Associated to the scholarship: 11/04682-3 - HIF1A inhibition in meduloblastoma cell line under hypoxia enviroment, BP.MS

Abstract

Medulloblastoma is the most common brain cancer in childhood. The treatment available is surgery, chemiotherapy and radiotherapy. The use of more effective therapy, which grants a greater free disease survival and less later related effects it is very wanted. Thus, the search of new therapeutic targets became very important for childhood treatment. These targets can be related to cellular homeostatic regulations or epignetic mechanisms which confer more agressiveness and lethality tumors. Genes like HIF1A (hypoxia inducible factor), VEGF (vascular endothelial growth factor, CA9 (carbonic anhidrase 9) and SLCA2A1 (glucose transporter) are related with a poor prognosis in many types of human cancers. HIF1A, when activated, begins the transcription of various genes related to metastasis and resistance to treatment. However, the regulation of HIF1A it still unclear. In this project we aim to assess the presence of epigenetic mechanisms in HIF1A expression and his target transcripts (VEGF, CA9 and SLC2A1). We intend to compare the methylation state and expression of these genes in distinct environments (hypoxia and normoxia). The methodology of this study includes HIF1A knockdown in cell line UW402 on hypoxia environment, pirosequencing and methylation array before/after gene inhibition. (AU)

Scientific publications

(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)

VEIGA CRUZEIRO, GUSTAVO ALENCASTRO; DOS REIS, MARISTELLA BERGAMO; SILVEIRA, VANESSA SILVA; PEIXOTO LIRA, REGIA CAROLINE; CARLOTTI, CARLOS GILBERTO; NEDER, LUCIANO; OLIVEIRA, RICARDO SANTOS; YUNES, JOSE ANDRES; BRANDALISE, SILVIA REGINA; AGUIAR, SIMONE; et al. HIF1A is Overexpressed in Medulloblastoma and its Inhibition Reduces Proliferation and Increases EPAS1 and ATG16L1 Methylation. CURRENT CANCER DRUG TARGETS, v. 18, n. 3, p. 287-294, 2018. (12/06592-4, 11/04682-3)