Screening radiation-induced differential expressed circular RNAs and establishing the expression models in human lymphoblastoid cell line AHH-1 induced by 60Co γ-rays

Abstract

After a large-scale radiological accident, such as Chernobyl or Fukushima Nuclear Power Plant accident occurred, rapid and high-throughput biodosimetry would be needed. It is very important to find a rapid, high-throughput biodosimeter for massive population triage and biological dose estimation. Studies showed that Circular RNA (circRNA) expressions can be altered by ionizing radiation in normal human cell lines and tumor tissue. Whether circRNAs are suitable for triage and dose estimation remains unclear. In this study, radiation-induced differential expressed circRNAs were screened through transcriptome sequencing with human lymphoblastoid cell line AHH-1 at 4 h after irradiated with 0, 2, and 5 Gy Cobalt-60 γ-rays. The results showed that 3 up-regulated and 4 down-regulated circRNAs were identified in 2 Gy-induced cells, and 5 up-regulated and 3 down-regulated circRNAs were identified in 5 Gy-induced cells both compared with those in the 0 Gy group. After validation, 11 circRNAs were chosen for establishing the expression dosimetry models, because their expression levels changed in a dose-dependent manner. Different circRNA expression models involving one or two circRNAs were established by stepwise regression analysis for different time-point (4h, 12 h, 24 h, and 48 h) post-irradiation, with R2 ranged from 0.950 to 0.998 (P < 0.01). A blind test showed that most of the estimated doses based on the expression models were deviated from the actual absorbed doses and the relative deviation were higher than 20%. In conclusion, ionizing radiation can alter the circRNA expression profile in the normal cell line AHH-1. Some circRNAs may be having the potential for being radiation biomarkers and needs further comprehensive investigation.