Fengxian District Center Hospital Graduate Student Training Base, Jinzhou Medical University, 201499 Shanghai, China.
Endoscopy Center, Minhang Hospital, Fudan University, 201199 Shanghai, China.
Front Biosci (Landmark Ed). 2024 Oct 12;29(10):351. doi: 10.31083/j.fbl2910351.
Gastric cancer (GC) is a significant global health burden with limited treatment options. The purpose of this study was to investigate the role of , a zinc transporter, in GC development and its capacity as a target for therapy.
A comprehensive analysis of GC datasets (GSE54129 and stomach adenocarcinoma (STAD) from The Cancer Genome Atlas (TCGA)) was conducted using bioinformatics tools to examine differential gene expression, focusing on . Functional assays, including Cell counting kit-8 (CCK-8) and transwell assays, were carried out on GC cell lines to determine the impact of knockdown on cell behavior. Flow cytometry was utilized to quantitatively observe cell apoptosis and cell cycle progression. The impact of zinc sulfate (ZnSO) on GC cells was evaluated by detecting apoptosis markers, Wnt/β-catenin signaling pathway activity, and oxidative stress biomarkers, focusing on the regulatory effect of overexpression.
Our analysis revealed significant upregulation of in GC samples compared to normal samples, and high expression was linked to poor prognosis. knockdown repressed proliferation, invasion, and migration of GC cells, induced apoptosis, as well as arrested the cell cycle. Additionally, ZnSO treatment induced cytotoxicity and oxidative stress in GC cells, while overexpression rescued ZnSO-induced, migration, invasion, and proliferation. Moreover, ZnSO4 had been shown to bolster apoptosis and trigger the Wnt/β-catenin signaling pathway, effects which were mitigated by the overexpression of .
Our results implied that was essential for GC progression by modulating zinc homeostasis and cellular processes. Targeting or zinc signaling may represent a potential therapeutic approach for GC treatment.
胃癌（GC）是一个具有全球性健康负担的重要疾病，治疗选择有限。本研究旨在探讨锌转运体 在 GC 发展中的作用及其作为治疗靶点的潜力。
使用生物信息学工具对 GC 数据集（GSE54129 和 TCGA 中的胃腺癌（STAD））进行综合分析，重点研究 的差异基因表达。在 GC 细胞系上进行细胞计数试剂盒-8（CCK-8）和 Transwell 测定等功能测定，以确定 敲低对细胞行为的影响。流式细胞术用于定量观察细胞凋亡和细胞周期进程。通过检测凋亡标志物、Wnt/β-catenin 信号通路活性和氧化应激生物标志物来评估硫酸锌（ZnSO）对 GC 细胞的影响，重点研究 过表达的调节作用。
我们的分析表明，与正常样本相比，GC 样本中 的表达显著上调，高表达与预后不良相关。 敲低抑制 GC 细胞的增殖、侵袭和迁移，诱导细胞凋亡并阻滞细胞周期。此外，ZnSO 处理诱导 GC 细胞的细胞毒性和氧化应激，而过表达 则可挽救 ZnSO 诱导的细胞迁移、侵袭和增殖。此外，已经表明 ZnSO4 可以增强凋亡并触发 Wnt/β-catenin 信号通路，而过表达则可以减轻这些作用。
我们的结果表明， 通过调节锌稳态和细胞过程在 GC 进展中起关键作用。靶向 或锌信号可能代表 GC 治疗的一种潜在治疗方法。
