Ma Zhanchuan, Dang Rongjing, Wu Guodong
Central Laboratory, Lequn Branch, The First Hospital of Jilin University, Changchun, Jilin, China.
Department of Cardiology, Lequn Branch, The First Hospital of Jilin University, Changchun, Jilin, China.
PLoS One. 2025 Jun 24;20(6):e0325213. doi: 10.1371/journal.pone.0325213. eCollection 2025.
Ataxia telangiectasia mutated (ATM) blockage can induce apoptosis in ovarian cancer. However, the molecular mechanisms underlying this process remain poorly understood. In this study, ovarian cancer cells (SKOV3) were treated with an ATM inhibitor (KU60019) for 24 hours, and the fold changes of DGAT1 and hsa-miR-1273g-3p were quantified by real-time quantitative polymerase chain reaction (RT-qPCR). Gene Ontology (GO) and pathway enrichment analyses of DGAT1-associated functions were performed. Hsa-miR-1273g-3p mimics were used to investigate the relationship between DGAT1 and hsa-miR-1273g-3p in ovarian cancer cells under ATM inhibitor treatment, and cell apoptosis rate, viability, and migration were detected. The DGAT1 inhibitor reversed KU60019-induced migration impairment in SKOV3 cells. Finally, Kaplan-Meier analysis showed the correlation between DGAT1 level and survival in ovarian cancer patients. We found that ATM blockage significantly suppressed hsa-miR-1273g-3p level and elevated DGAT1 level in SKOV3 cells. DGAT1 was enriched in cytokine receptor interaction, T cell receptor signaling pathway, and cell apoptosis. Hsa-miR-1273g-3p mimics reversed suppression of DGAT1 and impaired cell viability induced by KU60019. Higher levels of DGAT1 associated with worse survival in ovarian cancer patients. KU60019 induced ovarian cancer cell impairment by enhancing DGAT1 level and suppressing hsa-miR-1273g-3p level. Our results demonstrate the antitumor effect of KU60019 in ovarian cancer depended on miR1273g-3p/DGAT1 axis.
共济失调毛细血管扩张症突变基因（ATM）阻断可诱导卵巢癌细胞凋亡。然而，这一过程背后的分子机制仍知之甚少。在本研究中，用ATM抑制剂（KU60019）处理卵巢癌细胞（SKOV3）24小时，通过实时定量聚合酶链反应（RT-qPCR）对二酰甘油酰基转移酶1（DGAT1）和人微小RNA-1273g-3p（hsa-miR-1273g-3p）的倍数变化进行定量。对DGAT1相关功能进行基因本体论（GO）和通路富集分析。使用hsa-miR-1273g-3p模拟物研究在ATM抑制剂处理下卵巢癌细胞中DGAT1与hsa-miR-1273g-3p之间的关系，并检测细胞凋亡率、活力和迁移情况。DGAT1抑制剂逆转了KU60019诱导的SKOV3细胞迁移损伤。最后，Kaplan-Meier分析显示了DGAT1水平与卵巢癌患者生存率之间的相关性。我们发现，ATM阻断显著抑制SKOV3细胞中hsa-miR-1273g-3p水平并提高DGAT1水平。DGAT1在细胞因子受体相互作用、T细胞受体信号通路和细胞凋亡中富集。hsa-miR-1273g-3p模拟物逆转了KU60019诱导的DGAT1抑制和细胞活力损伤。DGAT1水平较高与卵巢癌患者较差的生存率相关。KU60019通过提高DGAT1水平和抑制hsa-miR-1273g-3p水平诱导卵巢癌细胞损伤。我们的结果表明，KU60019在卵巢癌中的抗肿瘤作用依赖于miR1273g-3p/DGAT1轴。
