Wang Zeyuan, Ran Xianting, Qian Siyu, Hou Huting, Dong Meng, Wu Shaoxuan, Ding Mengjie, Zhang Yue, Zhang Xudong, Zhang Mingzhi, Chen Qingjiang
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, China.
Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, China.
Arch Biochem Biophys. 2021 Oct 15;710:108998. doi: 10.1016/j.abb.2021.108998. Epub 2021 Jul 17.
Glycoprotein non-metastatic melanoma protein B (GPNMB) has been confirmed to be related to the pathogenesis of tumors. However, the potential impact of GPNMB on the progression of diffuse large B-cell lymphoma (DLBCL) is unclear. In this study, the expression levels of GPNMB and Yes-associated protein (YAP) were analyzed using qRT-PCT and Western blot assay. Cell counting kit-8, EdU, and flow cytometry assays were used to detect the proliferation and apoptosis of DLBCL cells. A nude mice xenograft model was established for in vivo research. Results showed that GPNMB and YAP1 were upregulated in DLBCL cell lines. Knockdown of GPNMB inhibited cell proliferation and promoted apoptosis in DLBCL cells. Additionally, the expression levels of YAP1 and the downstream effector of Hippo pathway (c-myc) were markedly decreased when GPNMB was knocked down. Moreover, knockdown of GPNMB inhibited the nuclear translocation of β-catenin protein, which could be abolished by YAP1 overexpression. Simultaneously, the anti-proliferative and pro-apoptotic effects of GPNMB knockdown could be reversed by YAP1 overexpression or LiCl (the activator of Wnt/β-catenin pathway). Furthermore, the mice xenograft model confirmed that inhibition of GPNMB restrained the tumorigenesis of DLBCL in vivo. In conclusion, GPNMB could partly activate the Wnt/β-catenin signaling pathway by targeting YAP1, so as to participate in tumorigenesis of DLBCL.
糖蛋白非转移性黑色素瘤蛋白B（GPNMB）已被证实与肿瘤的发病机制有关。然而，GPNMB对弥漫性大B细胞淋巴瘤（DLBCL）进展的潜在影响尚不清楚。在本研究中，使用qRT-PCT和蛋白质免疫印迹法分析了GPNMB和Yes相关蛋白（YAP）的表达水平。采用细胞计数试剂盒-8、EdU和流式细胞术检测DLBCL细胞的增殖和凋亡。建立裸鼠异种移植模型进行体内研究。结果显示，GPNMB和YAP1在DLBCL细胞系中上调。敲低GPNMB可抑制DLBCL细胞的增殖并促进其凋亡。此外，敲低GPNMB时，YAP1和Hippo通路的下游效应因子（c-myc）的表达水平显著降低。此外，敲低GPNMB可抑制β-连环蛋白的核转位，而YAP1过表达可消除这种抑制作用。同时，YAP1过表达或LiCl（Wnt/β-连环蛋白通路的激活剂）可逆转GPNMB敲低的抗增殖和促凋亡作用。此外，小鼠异种移植模型证实，抑制GPNMB可在体内抑制DLBCL的肿瘤发生。总之，GPNMB可通过靶向YAP1部分激活Wnt/β-连环蛋白信号通路，从而参与DLBCL的肿瘤发生。
