Elucidation of the genetic and epigenetic landscape alterations in RNA binding proteins in glioblastoma
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Shruti Bhargava1,*, Vikas Patil1,2,*, Kulandaivelu Mahalingam2, Kumaravel Somasundaram1
1Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore-560012, India
2Department of Bio-Medical Sciences, School of Biosciences and Technology, VIT University, Vellore-632014, India
*These authors have contributed equally to this work
Kumaravel Somasundaram, email: firstname.lastname@example.org
Keywords: glioblastoma, RNA binding proteins, regulation, signature, cancer stem cells
Received: April 15, 2016 Accepted: November 30, 2016 Published: December 27, 2016
RNA binding proteins (RBPs) have been implicated in cancer development. An integrated bioinformatics analysis of RBPs (n = 1756) in various datasets (n = 11) revealed several genetic and epigenetically altered events among RBPs in glioblastoma (GBM). We identified 13 mutated and 472 differentially regulated RBPs in GBM samples. Mutations in AHNAK predicted poor prognosis. Copy number variation (CNV), DNA methylation and miRNA targeting contributed to RBP differential regulation. Two sets of differentially regulated RBPs that may be implicated in initial astrocytic transformation and glioma progression were identified. We have also identified a four RBP (NOL3, SUCLG1, HERC5 and AFF3) signature, having a unique expression pattern in glioma stem-like cells (GSCs), to be an independent poor prognostic indicator in GBM. RBP risk score derived from the signature also stratified GBM into low-risk and high-risk groups with significant survival difference. Silencing NOL3, SUCLG1 and HERC5 inhibited GSC maintenance. Gene set enrichment analysis of differentially regulated genes between high-risk and low-risk underscored the importance of inflammation, EMT and hypoxia in high-risk GBM. Thus, we provide a comprehensive overview of genetic and epigenetic regulation of RBPs in glioma development and progression.
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