Transcriptional regulatory network response of A549 cells to heavy ion irradiation

The therapeutic effects of radiotherapy can be affected by cancer cells responding adaptively. The physical and biological characteristics of heavy ion beams make them ideal for use in radiotherapy. Cancer response to heavy ion therapy, however, remains unclear. Using ATAC-seq and RNA-seq analysis of A549 cells treated with heavy ions and IOX1 inhibitors, we determined the chromatin accessibility landscape of non-small cell lung cancer (NSCLC) cell line A549 after treatment.Alterations in chromatin accessibility caused by heavy ion treatments were occurred most often in promoter, intron and 5UTR regions of differentially expressed genes. We further identified CTCF as a key transcription factor in response to heavy ion therapy. The target genes regulated by CTCF were involved in the cell cycle and DNA damage repair pathway. Meanwhile, the chromatin accessibility changes induced by heavy ions were clearly different from those induced by chemosensitizer. And the difference in chromatin accessibility between LET30 and LET50 heavy ion was mostly different in degree, indicating a LETdependent effect of heavy ions on the regulation of gene transcription by changing chromatin accessibility. A valuable contribution to understanding gene regulatory networks and the biological effects of heavy ion therapy is provided by our study.