title: Elucidation of the genetic and epigenetic landscape alterations in RNA binding proteins in glioblastoma.
abstract: 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.
authors.affiliation: Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore-560012, India.
authors.forename: Shruti
authors.initials: S
authors.lastname: Bhargava
authors.affiliation: Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore-560012, India.|Department of Bio-Medical Sciences, School of Biosciences and Technology, VIT University, Vellore-632014, India.
authors.forename: Vikas
authors.initials: V
authors.lastname: Patil
authors.affiliation: Department of Bio-Medical Sciences, School of Biosciences and Technology, VIT University, Vellore-632014, India.
authors.forename: Kulandaivelu
authors.initials: K
authors.lastname: Mahalingam
authors.affiliation: Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore-560012, India.
authors.forename: Kumaravel
authors.initials: K
authors.lastname: Somasundaram
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D044127:Epigenesis, Genetic; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D014411:Neoplastic Stem Cells; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D016601:RNA-Binding Proteins; D012313:RNA
keywords: RNA binding proteins; cancer stem cells; glioblastoma; regulation; signature