Scientific Reports: Genomic analyses of early responses to radiation in glioblastoma reveal new alterations at transcription, splicing, and translation levels
Choudhary Saket, Suzanne C Burns, Mirsafian Hoda, Wenzheng Li, Dat T Vo, Qiao Mei, Lei Xiufen, Andrew D Smith, Luiz O Penalva
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 …
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