Wang Ning, Yu Miaomiao, Fu Yan, Ma Zhanchuan
Central Laboratory, The First Hospital of Jilin University, Changchun, China.
Department of Gynaecology II, The First Hospital of Jilin University, Changchun, China.
Front Oncol. 2022 Jun 20;12:839508. doi: 10.3389/fonc.2022.839508. eCollection 2022.
Blocking ataxia telangiectasia mutated (ATM), a crucial player in DNA repair responses, has been proposed as a promising strategy in anti-cancer therapy. Most previous studies have focused on DNA damage response-related pathways after administration of ATM inhibitors. However, ATM inhibition could potentially influence a wide range of changes in gene expression, which remain poorly defined. Here, we report that administration of the ATM inhibitor KU60019 led to impaired migration and enhanced apoptosis in the ovarian cancer cell line SKOV3, accompanied by abnormally elevated O-GlcNAc transferase and O-GlcNAcase expression levels. In addition, KU60019 treatment significantly suppressed expression of in SKOV3 cells. Up-regulation of expression inhibited increases in OGT and OGA level, and reversed the effects of ATM inhibition on apoptosis and migration in SKOV3 cells. Finally, we found aberrant expression of and to be associated with ovarian cancer patient survival. Taken together, our results suggest that ATM inhibition may promote SKOV3 cell apoptosis suppressing and elevating and expression, providing new insights into the application of ATM inhibitors in cancer immunotherapy.
阻断共济失调毛细血管扩张症突变基因（ATM），这是DNA修复反应中的关键因子，已被提议作为抗癌治疗的一种有前景的策略。以往大多数研究集中在给予ATM抑制剂后与DNA损伤反应相关的途径。然而，ATM抑制可能会潜在地影响基因表达的广泛变化，而这些变化仍不清楚。在此，我们报告给予ATM抑制剂KU60019导致卵巢癌细胞系SKOV3的迁移受损和凋亡增强，同时伴有O-连接N-乙酰葡糖胺转移酶（OGT）和O-连接N-乙酰葡糖胺酶（OGA）表达水平异常升高。此外，KU60019处理显著抑制SKOV3细胞中[此处原文缺失具体基因名称]的表达。[此处原文缺失具体基因名称]表达的上调抑制了OGT和OGA水平的增加，并逆转了ATM抑制对SKOV3细胞凋亡和迁移的影响。最后，我们发现[此处原文缺失具体基因名称]和[此处原文缺失具体基因名称]的异常表达与卵巢癌患者的生存相关。综上所述，我们的结果表明，ATM抑制可能通过抑制[此处原文缺失具体基因名称]并提高[此处原文缺失具体基因名称]和[此处原文缺失具体基因名称]的表达来促进SKOV3细胞凋亡，为ATM抑制剂在癌症免疫治疗中的应用提供了新的见解。
