Clinical Research Center, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Biochim Biophys Acta Mol Basis Dis. 2022 Dec 1;1868(12):166492. doi: 10.1016/j.bbadis.2022.166492. Epub 2022 Jul 16.
SUMO-specific proteases (SENPs) play pivotal roles in maintaining the balance of SUMOylation/de-SUMOylation and in SUMO recycling. Deregulation of SENPs leads to cellular dysfunction and corresponding diseases. As a key member of the SENP family, SENP1 is highly correlated with various cancers. However, the potential role of SENP1 in leukemia, especially in acute lymphoblastic leukemia (ALL), is not clear. This study shows that ALL cells knocking down SENP1 display compromised growth rather than significant alterations in chemosensitivity, although ALL relapse samples have a relatively higher expression of SENP1 than the paired diagnosis samples. Camptothecin derivatives 7-ethylcamptothecin (7E-CPT, a monomer compound) and topotecan (TPT, an approved clinical drug) induce specific SENP1 reduction and severe apoptosis of ALL cells, showing strong anticancer effects against ALL. Conversely, SENP1 could attenuate this inhibitory effect by targeting DNA topoisomerase I (TOP1) for de-SUMOylation, indicating that specific reduction in SENP1 induced by 7E-CPT and/or topotecan inhibits the proliferation of ALL cells.
SUMO 特异性蛋白酶（SENPs）在维持 SUMO 化/去 SUMO 化平衡和 SUMO 循环中发挥关键作用。SENPs 的失调会导致细胞功能障碍和相应的疾病。作为 SENP 家族的关键成员，SENP1 与多种癌症高度相关。然而，SENP1 在白血病，特别是急性淋巴细胞白血病（ALL）中的潜在作用尚不清楚。本研究表明，敲低 SENP1 的 ALL 细胞显示出生长受损，而不是对化学敏感性的显著改变，尽管 ALL 复发样本的 SENP1 表达相对高于配对的诊断样本。喜树碱衍生物 7-乙基喜树碱（7E-CPT，一种单体化合物）和拓扑替康（TPT，一种已批准的临床药物）诱导 ALL 细胞中特定的 SENP1 减少和严重凋亡，对 ALL 具有强烈的抗癌作用。相反，SENP1 可以通过靶向 DNA 拓扑异构酶 I（TOP1）进行去 SUMO 化来减弱这种抑制作用，表明 7E-CPT 和/或拓扑替康特异性降低 SENP1 抑制 ALL 细胞的增殖。
