Tumor-associated long non-coding RNAs show variable expression across diffuse gliomas and effect on cell growth upon silencing in glioblastoma

Long noncoding RNAs (lncRNAs) have been recently recognized as critical components of cancer biology linked to oncogenic processes. Certain lncRNAs are known to act as oncogenes, and the disease-specific expression of many lncRNAs makes them informative biomarkers. We identified 22 uncharacterized lncRNAs from RNA-seq data of 169 glioblastoma (GBM) tumor samples sequenced by The Cancer Genome Atlas (TCGA) consortium and studied their expression in TCGA diffuse glioma cohort including also IDH-mutant astrocytomas and oligodendrogliomas as well as in normal brain samples from the Genotype-Tissue Expression cohort. All of the 22 lncRNAs were clearly upregulated in diffuse gliomas samples compared to the normal brain. Interestingly, 20 (91%) of these lncRNAs had significant expression differences between tumor grades and/or entities, and 14 (64%) were associated with overall patient survival. All 22 lncRNAs were expressed in at least one of the studied GBM cell lines and 10 (45%) were expressed in all four. When six of the lncRNAs were silenced in the SNB19 GBM cell line, the knock-down was associated with reduced growth and colony formation for three lncRNAs: TCONS_l2_00001282, lnc-GBMT-6, and lnc-NBN-1. In conclusion, the studied lncRNAs are associated with survival in patients with diffuse glioma and have functional relevance in GBM.