Investigating Epigenetic Dysregulation of Long Non-Coding RNAs in Glioblastoma and Glioma Stem Cells

Investigating Epigenetic Dysregulation of Long Non-Coding RNAs in Glioblastoma and Glioma Stem Cells

Alvin Sherman Library

Glioblastoma multiforme (GBM) or Grade IV glioma is a very aggressive form of brain tumor with an overall survival rate of 15 months. The tumor contains glioma stem cells (GSCs) that are resistant to existing therapies. Long non-coding RNAs such as DNA methylation are implicated in epigenetic dysregulation of GBM and GSCs. In this study, we screened lncRNAs with altered DNA methylation in both tumor cells and GSCs compared to normal neural cells using 450K methylation array data. We identified 508 methylation sites (320 lncRNAs) that were either hypermethylated (or gained methylation) or hypomethylated (lost methylation) in GBM and GSCs. Of the 320 lncRNAs, 134 were hypomethylated and 186 were hypermethylated in both the tumor and stem cells compared to normal neural cells. Moreover of the 320 lncRNAs, 44 of them were correlated to their expression and clinical prognosis of patients. Of the 44 lncRNAs, we chose 9 hypomethylated lncRNAs to assess expressions using quantitative reverse transcription PCR (qRTPCR) in four GSC lines. The goal of this study is to develop these lncRNAs as the therapeutic targets of GBM.