Transcriptome alteration spectrum in rat lung induced by radiotherapy

放射治疗诱导的大鼠肺转录组改变谱

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Abstract

Radiation therapy is crucial for curative treatment of lung cancer, which frequently leads to lung injury. Long non-coding RNAs (lncRNAs) are a group of RNAs longer than 200 nucleotides and lack protein-coding capacity. Increasing evidences demonstrate the important roles of lncRNAs in biological processes. However, the mechanism underlying the association of ionizing radiation with alterations in mRNA and lncRNA expression and lung injury remains unclear. In our study, the male Sprague-Dawley (SD) rats were exposed to a dose of 18 Gy of 6 MV X-ray and the transcriptome spectrum was studied. To identify the differentially expressed mRNAs and lncRNAs induced by X-ray, the RNA sequencing data of lung tissues from irradiated and normal rats for 4, 8, and 16 weeks were analyzed, using |log2_ratio| ≥ 1 and q ≤ 0.05 as thresholds for significantly differential expression. The number of differentially expressed mRNAs was 1097 (686 up- and 411 down-) for 4-week radiotherapy group, 3006 (1935 up- and 1071 down-) for 8-week group and 1838 (1178 up- and 660 down-) for 16-week group. There were 606 (279 up- and 327 down-) differentially expressed lncRNAs in 4-week group, 1715 (831 up- and 884 down-) in 8-week group and 1043 (656 up- and 387 down-) in 16-week group. The differentially expressed mRNAs were mainly involved in cell cycle regulation and Fc receptor pathway, while the lncRNA target genes were significantly enriched in cellular stress response and regulation of cell migration. Moreover, compared with the control group, the irradiated group presented higher tissue specificity of lncRNAs. Radiation-induced lung injury, especially the dynamic network of lncRNAs and mRNAs, is worthy of study. Investigation on the regulatory details of related pathways is significant for the prevention of radiation-related lung injury, as well as the improvement of radiation therapy.

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