Choudhary et al. 2019 (PRJNA591767)

General Details

Title Integrated analyses of early responses to radiation in glioblastoma identify new alterations in RNA processing and candidate targets to improve treatment outcomes
Organism
Number of Samples 17
Release Date 2019/11/26 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP233276
ENA SRP233276
GEO
BioProject PRJNA591767

Publication

Title
Authors Choudhary S,Burns SC,Mirsafian H,Li W,Vo DT,Qiao M,Lei X,Smith AD,Penalva LO
Journal Scientific reports
Publication Date 2020 Jun 2
Abstract High-dose radiation is the main component of glioblastoma therapy. Unfortunately, radio-resistance is a common problem and a major contributor to tumor relapse. Understanding the molecular mechanisms driving response to radiation is critical for identifying regulatory routes that could be targeted to improve treatment response. We conducted an integrated analysis in the U251 and U343 glioblastoma cell lines to map early alterations in the expression of genes at three levels: transcription, splicing, and translation in response to ionizing radiation. Changes at the transcriptional level were the most prevalent response. Downregulated genes are strongly associated with cell cycle and DNA replication and linked to a coordinated module of expression. Alterations in this group are likely driven by decreased expression of the transcription factor FOXM1 and members of the E2F family. Genes involved in RNA regulatory mechanisms were affected at the mRNA, splicing, and translation levels, highlighting their importance in radiation-response. We identified a number of oncogenic factors, with an increased expression upon radiation exposure, including BCL6, RRM2B, IDO1, FTH1, APIP, and LRIG2 and lncRNAs NEAT1 and FTX. Several of these targets have been previously implicated in radio-resistance. Therefore, antagonizing their effects post-radiation could increase therapeutic efficacy. Our integrated analysis provides a comprehensive view of early response to radiation in glioblastoma. We identify new biological processes involved in altered expression of various oncogenic factors and suggest new target options to increase radiation sensitivity and prevent relapse.
PMC PMC7265345
PMID 32488114
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR10533453 PRJNA591767 Homo sapiens U2OS Ribo-Seq
SRR10533454 PRJNA591767 Homo sapiens U2OS Ribo-Seq
SRR10533455 PRJNA591767 Homo sapiens U2OS Ribo-Seq
SRR10533456 PRJNA591767 Homo sapiens U2OS Ribo-Seq
SRR10533457 PRJNA591767 Homo sapiens U2OS Ribo-Seq
SRR10533458 PRJNA591767 Homo sapiens U2OS Ribo-Seq
SRR10533459 PRJNA591767 Homo sapiens U2OS Ribo-Seq
SRR10533460 PRJNA591767 Homo sapiens U2OS Ribo-Seq
SRR10533461 PRJNA591767 Homo sapiens U343 Ribo-Seq
SRR10533462 PRJNA591767 Homo sapiens U343 Ribo-Seq
SRR10533463 PRJNA591767 Homo sapiens U343 Ribo-Seq
SRR10533464 PRJNA591767 Homo sapiens U343 Ribo-Seq
SRR10533465 PRJNA591767 Homo sapiens U343 Ribo-Seq
SRR10533466 PRJNA591767 Homo sapiens U343 Ribo-Seq
SRR10533467 PRJNA591767 Homo sapiens U343 Ribo-Seq
SRR10533468 PRJNA591767 Homo sapiens U343 Ribo-Seq
SRR10533469 PRJNA591767 Homo sapiens U343 Ribo-Seq
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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