Li Ying, Wang Wei, Sun Lingjie, Huang Junxia, Ma Xiaolin, Li Saisai, Shi Xue
Department of Hematology, The Affiliated Hospital of Qingdao University, Qingdao University, No. 16 Jiangsu Road, Qingdao, 266000, Shandong Province, China.
J Mol Histol. 2024 Dec 26;56(1):54. doi: 10.1007/s10735-024-10323-0.
A poorer prognosis is thought to be associated with "double expressor lymphomas," which are a subtype of diffuse large B cell lymphomas (DLBCL) that co-express MYC and BCL2. While the role of ubiquitin-specific peptidase 37 (USP37) in lung cancer, where it mediates the deubiquitination and stabilization of c-myc, has been well-documented, its involvement in DLBCL remains unexplored. The use of RT-PCR, immunohistochemistry, or WB test allowed for the detection of elevated USP37 in DLBCL tissues and cells. In order to understand the function of USP37 in DLBCL, keloid DLBCL cells were transfected with si-USP37 using Lipofectamine 3000. When tested on DLBCL cells, USP37 increased cell proliferation and inhibited cell cycle progression. USP37 controls the process of deubiquitination to stabilise c-myc proteins. The overexpression of c-Myc facilitated cell proliferation and prevented the cell cycle of DLBCL cells stimulated by si-USP37, which should be taken into consideration. Furthermore, USP37 depletion consistently hinders the development of tumour xenografts in mouse models. Overexpressing c-myc, however, may partially counteract this impact. The data show that USP37 may be a potential therapeutic target for DLBCL, and that it may enhance the course of the disease by deubiquitinating c-myc via direct interactions with c-myc.
较差的预后被认为与“双表达淋巴瘤”有关,“双表达淋巴瘤”是弥漫性大B细胞淋巴瘤(DLBCL)的一种亚型,其共同表达MYC和BCL2。虽然泛素特异性肽酶37(USP37)在肺癌中通过介导c-myc的去泛素化和稳定化发挥作用,这一点已有充分记录,但其在DLBCL中的作用仍未得到探索。使用逆转录聚合酶链反应(RT-PCR)、免疫组织化学或蛋白质免疫印迹(WB)检测发现,DLBCL组织和细胞中USP37水平升高。为了了解USP37在DLBCL中的功能,使用Lipofectamine 3000将瘢痕疙瘩样DLBCL细胞转染si-USP37。在DLBCL细胞上进行检测时,USP37可促进细胞增殖并抑制细胞周期进程。USP37通过控制去泛素化过程来稳定c-myc蛋白。应考虑到,c-Myc的过表达促进了细胞增殖,并阻止了由si-USP37刺激的DLBCL细胞的细胞周期。此外,在小鼠模型中,USP37的缺失持续阻碍肿瘤异种移植的发展。然而,过表达c-myc可能会部分抵消这种影响。数据表明,USP37可能是DLBCL的一个潜在治疗靶点,并且它可能通过与c-myc直接相互作用使c-myc去泛素化,从而加重疾病进程。