Background:
Radiotherapy is one of the most effective therapeutic strategies for
cervical cancer patients, although radioresistance-mediated residual and recurrent
tumors are the main cause of treatment failure. However, the mechanism of
tumor radioresistance is still elusive. DNA damage response pathways are key determinants of radioresistance. The purpose of this study was to investigate the role and mechanism of SND1 in radioresistance of
cervical cancer. Methods: A stable HeLa cell line with SND1 knockout (HeLa-KO) was generated through a modified CRISPR/Cas9 double-nicking gene editing system. The stable CaSki cell lines with SND1 knockdown (CaSki-Ctrl, CaSki-SND1-sh-1, CaSki-SND1-sh-2) were constructed through lentivirus transfection with the pSil-SND1-sh-1 and pSil-SND1-sh-2 plasmids. Results: It was observed that SND1 deficiency significantly increased the radiosensitivity of
cervical cancer cells. It was also found that silencing SND1 promotes radiation-induced apoptosis. Significantly, the cells with a loss of SND1 function exhibited inefficient
ataxia telangiectasia mutated pathway activation, subsequently impairing DNA repair and G2/M checkpoint arrest. In addition,
threonine 103 is an important phosphorylation site of SND1 under
DNA damaging stress. Conclusion: Collectively, the results of this study reveal a potent
radiosensitizing effect of silencing SND1 or T103 mutation on
cervical cancer cells, providing novel insights into potential therapeutic strategies for
cervical cancer treatment.