The Long Non-Coding RNA Promotes Proliferation of Glioma Stem Cells and Modulates Their Inflammation Pathway Mainly through Post-Transcriptional Regulation.

Glioblastomas represent approximatively half of all gliomas and are the most deadly and aggressive form. Their therapeutic resistance and tumor relapse rely on a subpopulation of cells that are called Glioma Stem Cells (GSCs). Here, we investigated the role of the long non-coding RNA in GSC biology using descriptive and functional analyses of glioma samples classified according to their isocitrate dehydrogenase () gene mutation status, and of GSC lines. We found that is overexpressed only in aggressive () glioma and GSC lines. ShRNA-based depletion of in GSCs decreased cell proliferation and altered the expression of several hundreds of genes. Integrative analysis revealed that these expression changes were not associated with changes in DNA methylation or chromatin signatures at the promoter of the majority of genes deregulated following silencing in GSCs, suggesting a post-transcriptional regulation. In addition, transcription factor binding motif enrichment and correlation analyses indicated that affects, directly or indirectly, the expression of key transcription factors implicated in GCS biology, including E2F8, E2F1, STAT1, and ATF3, thus contributing to GCS aggressiveness by promoting their proliferation and modulating the inflammation pathway.