Department of Critical Care Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, Henan province, PR China.
Department of Pulmonary and Critical Care Medicine, Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian province, PR China.
Exp Cell Res. 2021 Dec 15;409(2):112911. doi: 10.1016/j.yexcr.2021.112911. Epub 2021 Nov 8.
G protein nucleolar 3 (GNL3), which acts as an oncoprotein in various carcinomas, is associated with tumor progression; however, little is known regarding GNL3 function in non-Hodgkin lymphoma (NHL). In this study, we first used in silico analysis to determine associations between GNL3 and diffuse large B-cell lymphoma (DLBCL). We then examined the effect of GNL3 on NHL progression, including cell proliferation, apoptosis, and cell cycle progression, and determined its underlying molecular mechanism using in vitro lymphoma cell lines and in vivo mouse xenograft models. We found that GNL3 mRNA levels were markedly higher in DLBCL tissues than in normal tissues, with these higher levels associated with poor prognosis. Additionally, GNL3 overexpression promoted NHL cell proliferation and cell cycle progression and reduced apoptosis in vitro, and enhanced tumorigenesis in an in vivo xenograft model. Moreover, we found that GNL3 upregulated the levels of Wnt/β-catenin signaling pathway-related factors and downstream target genes, whereas the opposite result was observed in GNL3-silenced cells. Furthermore, a rescue experiment using a Wnt/β-catenin inhibitor (XAV939) confirmed that GNL3 promotes NHL progression by activating the Wnt/β-catenin signaling pathway. These findings demonstrated that GNL3 functions as an oncogenic driver in NHL via the Wnt/β-catenin pathway.
G 蛋白核仁 3（GNL3）作为多种癌中的癌蛋白，与肿瘤进展有关；然而，对于非霍奇金淋巴瘤（NHL）中 GNL3 的功能知之甚少。在这项研究中，我们首先使用计算机分析来确定 GNL3 与弥漫性大 B 细胞淋巴瘤（DLBCL）之间的关联。然后，我们研究了 GNL3 对 NHL 进展的影响，包括细胞增殖、凋亡和细胞周期进展，并使用体外淋巴瘤细胞系和体内小鼠异种移植模型确定了其潜在的分子机制。我们发现，与正常组织相比，DLBCL 组织中的 GNL3 mRNA 水平明显升高，这些较高水平与预后不良有关。此外，GNL3 过表达促进 NHL 细胞的增殖和细胞周期进展，减少体外凋亡，并增强体内异种移植模型中的肿瘤发生。此外，我们发现 GNL3 上调了 Wnt/β-catenin 信号通路相关因子和下游靶基因的水平，而在 GNL3 沉默细胞中则观察到相反的结果。此外，使用 Wnt/β-catenin 抑制剂（XAV939）的挽救实验证实，GNL3 通过激活 Wnt/β-catenin 信号通路促进 NHL 的进展。这些发现表明，GNL3 通过 Wnt/β-catenin 途径在 NHL 中作为致癌驱动因子发挥作用。
