Screening of early radiation-responsive long non-coding RNAs in human lymphoblastoid cells AHH-1 and a preliminary investigation of their potential for biodosimetry

PURPOSE: In nuclear and radiological emergencies, rapid and high-throughput screening of victims is essential for effective medical treatment. The biodosimeter based on transcriptomics holds great promise in triaging vast casualties fast by microarray and PCR. We aimed to screen early radiation-responsive long non-coding RNAs (lncRNAs) and preliminarily explore their potential for biodosimetry. METHODS: We screened radiation differentially expressed (DE) lncRNAs through whole transcriptome sequencing in AHH-1 cells at 4 h post-irradiation. The dose-response relationships for early radiation-responsive lncRNAs were confirmed at 4, 12, 24 and 48 h after exposure to 0, 1, 2, 4, 6, 8 and 12 Gy γ-rays by real-time polymerase chain reaction (real-time qPCR). Four lncRNAs including lnc-INTS8-5:3, MIR34AHG:10, PVT1:58 and LINC01759:20, were further validated using ex vivo irradiated peripheral whole blood from 15 healthy volunteers aged 20-29 at 4 h and 24 h post-exposure. LncRNA-based dose classification models were developed and verified by logistic regression and receiver operating characteristic (ROC) analysis. RESULTS: Fifteen early radiation-responsive lncRNAs were recognized in AHH-1 cells, of which 12 demonstrated a good dose-response relationship. lnc-INTS8-5:3, MIR34AHG:10, PVT1:58 and LINC01759:20 were significantly upregulated in ex vivo irradiated human blood. Notably, LINC01759:20 had extremely low spontaneous abundance but demonstrated a significant fold change of up to 65 after irradiation. The dose classification models can effectively classify '0 Gy vs. >0 Gy' and '<2 Gy vs. ≥2 Gy' (AUC = 0.806-1.000). The excellent performance of the built models in judging whether exposed or not was confirmed by leave-one-donor-out cross-validation (LODO-CV). CONCLUSIONS: Ionizing radiation (IR) can rapidly induce dose-dependent expression changes of lncRNAs in human lymphoblastoid cells AHH-1. Furthermore, certain early and highly radiation-responsive lncRNAs in human whole blood show promise as preliminary candidate biomarkers for radiation exposure.