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Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
Tumor-associated long non-coding RNAs show variable expression across diffuse gliomas and effect on cell growth upon
Joonas Uusi-Mäkelä1, Maria Kauppinen1,2, Janne Seppälä1
1Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Abstract:
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.
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