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

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)