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 和蛋白质印迹法分析了 GPNMB 和 Yes 相关蛋白 (YAP) 的表达水平。使用细胞计数试剂盒-8、EdU 和流式细胞术检测 DLBCL 细胞的增殖和凋亡。在体内建立裸鼠异种移植模型研究。结果显示 GPNMB 和 YAP1 在 DLBCL 细胞系中上调。GPNMB 的敲低抑制了 DLBCL 细胞的细胞增殖并促进了细胞凋亡。此外，当 GPNMB 被敲低时，YAP1 和 Hippo 通路下游效应子 (c-myc) 的表达水平显着降低。此外，GPNMB 的敲低抑制了 β-catenin 蛋白的核转位，这可以通过 YAP1 过表达来消除。同时，YAP1 过表达或 LiCl（Wnt/β-catenin 通路的激活剂）可以逆转 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 抑制了体内DLBCL 的肿瘤发生. 综上所述，GPNMB 可以通过靶向 YAP1 部分激活 Wnt/β-catenin 信号通路，从而参与 DLBCL 的肿瘤发生。