Differential radiation response between normal astrocytes and glioma cells revealed by comparative transcriptome analysis

Abstract

Normal astrocytes are more resistant to radiation than glioma cells. Radiation-resistant glioma cells and normal astrocytes usuallly share similar mechanisms of radioresistance. Investigation of the underlying mechanisms of differential radiation response between normal astrocytes and glioma cells is thus significant for improvement of glioma treatment. Here, we report on the differential radiation responses between normal astrocytes and glioma cells at the transcriptome level. Human astrocytes (HA) and U251 glioma cell lines were used as in vitro models. The transcriptome profiles of radiation-treated and nontreated HA and U251 cells were generated by next-generation sequencing. In total, 296 mRNAs and 224 lncRNAs in HA and 201 mRNAs and 107 lncRNAs in U251 were found to be differentially expressed after radiation treatment. Bioinformatics analyses indicated that radiation causes similar alterations in HA and U251 cells, while several key pathways involved in cancer development and radiation resistance, including P53, TGF-β, VEGF, Hippo and serotonergic synapse pathways, were oppositely regulated by radiation treatment, suggesting their important role in this process. Furthermore, we showed the critical role of Hippo/YAP signaling in radiation resistance of glioma cells. In summary, our findings revealed novel insights about differential responses between normal astrocytes and glioma cells. Our work suggested that YAP inhibitor could not be used in combination with radiation for glioma treatment.