He Jinsong, Huang Jing, Tang Guo, Wang Pan, He Ming, Wei Shoujiang
Department of Gastroenterology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People's Republic of China.
Lung Cancer Institute, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People's Republic of China.
Cancer Manag Res. 2022 Feb 17;14:659-672. doi: 10.2147/CMAR.S340053. eCollection 2022.
Zinc finger protein 154 () has been identified as a tumor suppressor gene in multiple carcinomas. Lymph node (LN) metastasis is one of the most intensively negative factor of gastric cancer (GC) prognosis. However, the potential mechanisms of ZNF154-mediated LN metastasis are not elucidated. This study aimed to investigate the role of ZNF154 in LN metastasis of GC and their underlying mechanisms through in vitro and in vivo experiments.
Antitumor effect was measured by growth inhibition by cell counting kit-8 (CCK-8) and colony formation assay. Cell cycle distribution and apoptosis were evaluated by flow cytometry. Cell migration and invasion were measured by wound healing and transwell invasion assays, respectively. The expression levels of proteins were analyzed by Western blot. Xenograft models were used for validation in vivo.
Our research showed that ZNF154 was down-regulated in 81.43% (57 of 70) of GC tissues compared with 58.6% of paired non-tumor tissues from patients, ZNF154 was down-regulated in 100% (7 of 7) of GC cell lines, up-regulated expression of ZNF154 in MGC-803 GC cells reduced cell proliferation, viability, migration and invasion, and enhanced cell apoptosis and arrested cell cycle in G2 phase, and suppressed tumorigenicity of MGC-803 cells in mice. Furthermore, up-regulated expression of ZNF154 mRNA reduced the expression of B-cell lymphoma-2 (Bcl-2), matrix metalloproteinase 2 (MMP-1), hepatocyte growth factor (HGF), vascular endothelial growth factor-A/C (VEGF-A/C).
ZNF154 inhibited LN metastasis of GC cells by suppressing several biological events of GC cells. ZNF154 was a tumor suppressor gene that is a promising target for blocking nodal involvement in GC.
锌指蛋白154（ZNF154）已被确定为多种癌症中的肿瘤抑制基因。淋巴结（LN）转移是胃癌（GC）预后最具负面影响的因素之一。然而，ZNF154介导LN转移的潜在机制尚未阐明。本研究旨在通过体外和体内实验探讨ZNF154在GC的LN转移中的作用及其潜在机制。
通过细胞计数试剂盒-8（CCK-8）和集落形成试验检测生长抑制来测定抗肿瘤作用。通过流式细胞术评估细胞周期分布和凋亡。分别通过伤口愈合试验和Transwell侵袭试验测量细胞迁移和侵袭。通过蛋白质印迹分析蛋白质的表达水平。异种移植模型用于体内验证。
我们的研究表明，与患者的58.6%配对非肿瘤组织相比，70例GC组织中有81.43%（57例）的ZNF154下调，7株GC细胞系中有100%（7株）的ZNF154下调，MGC-803 GC细胞中ZNF154的上调表达降低了细胞增殖、活力、迁移和侵袭，并增强了细胞凋亡并使细胞周期停滞在G2期，并抑制了MGC-803细胞在小鼠中的致瘤性。此外，ZNF154 mRNA的上调表达降低了B细胞淋巴瘤-2（Bcl-2）、基质金属蛋白酶2（MMP-1）、肝细胞生长因子（HGF）、血管内皮生长因子-A/C（VEGF-A/C）的表达。
ZNF154通过抑制GC细胞的几种生物学事件来抑制GC细胞的LN转移。ZNF154是一种肿瘤抑制基因，是阻断GC淋巴结受累的有希望的靶点。
