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Abstract：
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.
摘要：
这项研究通过比较SMARCD3在胃癌细胞系和组织中印戒细胞（SRC）和高分化（WD）组中的表达来研究SMARCD3在胃癌中的作用。与WD组相比，我们观察到SRC组的SMARCD3水平升高。通过SMARCD3敲入和敲除方法进行功能分析。Kaplan-Meier生存分析显示，SMARCD3较高的表达与胃癌患者总体生存较差相关（HR2.16，p<0.001）。SMARCD3敲除细胞显示增殖减少，迁移,入侵,和上皮间质转化（EMT）标志物的表达，与临时和稳定的SMARCD3过表达实验的结果相反，显示细胞面积增加和不规则性(p<0.001)。进一步分析显示SMARCD3在MKN-74细胞中的过表达显著增强p-AKT-S473和p-ERK水平(p<0.05),在KATOIII细胞中，它增加了β-catenin和PI3Kp85活性（p<0.05）。相反，SMARCD3耗竭后SNU601细胞中的这些活性降低。该研究得出结论，SMARCD3过表达由于其在促进EMT中的作用，可能是胃癌治疗中的阴性预后标志物和潜在治疗靶标。
