This study investigates the role of SMARCD3 in gastric cancer by comparing its expression in signet ring cell (SRC) and well-differentiated (WD) groups within gastric cancer cell lines and tissues. We observed elevated SMARCD3 levels in the SRC group compared to the WD group. Functional analysis was conducted through both SMARCD3 knock-in and knock-out methods. Kaplan–Meier survival analysis indicated that higher SMARCD3 expression correlates with poorer overall survival in gastric cancer patients (HR 2.16,p< 0.001). SMARCD3 knock-out cells showed decreased proliferation, migration, invasion, and expression of epithelial–mesenchymal transition (EMT) markers, contrasting with results from temporary and stable SMARCD3 overexpression experiments, which demonstrated increased cell area and irregularity (p< 0.001). Further analysis revealed that SMARCD3 overexpression in MKN-74 cells significantly enhanced p-AKT-S473 and p-ERK levels (p< 0.05), and in KATO III cells, it increased β-catenin and PI3Kp85 activities (p< 0.05). Conversely, these activities decreased in SNU 601 cells following SMARCD3 depletion. The study concludes that SMARCD3 overexpression may serve as a negative prognostic marker and a potential therapeutic target in gastric cancer treatment due to its role in promoting EMT.
本研究通过比较胃癌细胞系及组织中印戒细胞（SRC）与高分化（WD）组SMARCD3的表达水平，探讨其在胃癌中的作用机制。结果显示，SRC组SMARCD3表达显著高于WD组。通过SMARCD3基因敲入与敲除实验进行功能分析，Kaplan-Meier生存曲线表明SMARCD3高表达与胃癌患者较差的总生存期显著相关（风险比2.16，p<0.001）。SMARCD3敲除细胞表现出增殖、迁移、侵袭能力下降及上皮-间质转化（EMT）标志物表达降低，而瞬时与稳定过表达实验则显示细胞面积增大、形态不规则性增加（p<0.001）。进一步研究发现，MKN-74细胞中SMARCD3过表达显著提升p-AKT-S473与p-ERK水平（p<0.05），KATO III细胞中β-连环蛋白与PI3Kp85活性增强（p<0.05）；相反，SNU 601细胞在SMARCD3敲除后上述通路活性降低。本研究证实SMARCD3过表达通过促进EMT进程，可能作为胃癌不良预后的生物标志物及潜在治疗靶点。
SMARCD3 Overexpression Promotes Epithelial–Mesenchymal Transition in Gastric Cancer
肿瘤(癌症)患者之家