Background

The Na⁺/K⁺-ATPase alpha1 subunit (ATP1A1) is a critical component of Na⁺/K⁺-ATPase (NKA), a membrane pump that maintains a low intracellular Na⁺/K⁺ ratio and retains cellular volume and osmolarity. ATP1A1 was recently implicated in tumor behavior. Therefore, the present study investigated the role of ATP1A1 in patients with gastric cancer (GC).

Methods

Knockdown experiments were conducted on human GC cell lines using ATP1A1 siRNA, and its effects on proliferation, the cell cycle, apoptosis, and cellular movement were examined. Gene expression profiling was performed by a microarray analysis. Primary tumor samples from 192 GC patients who underwent gastrectomy were subjected to an immunohistochemical analysis.

Results

High ATP1A1 expression levels were observed in NUGC4 and MKN74 cells. Cell proliferation was suppressed and apoptosis was induced by the siRNA-induced knockdown of ATP1A1. The microarray analysis showed that knockdown of ATP1A1 leads to the up-regulated expression of genes involved in the interferon (IFN) signaling pathway, such as STAT1, STAT2, IRF1, and IRF9. Furthermore, the depletion of ATP1A1 altered the phosphorylation of the MAPK pathway. The immunohistochemical analysis revealed that the expression of ATP1A1 was associated with the histological type, venous invasion, and the pathological T stage. Furthermore, the prognostic analysis showed a relationship between high ATP1A1 expression levels and poor postoperative survival.

Conclusions

ATP1A1 appears to regulate tumor progression by altering IFN signaling, and high ATP1A1 expression levels were associated with poor postoperative survival in GC patients. The present results provide novel insights into the function of ATP1A1 as a mediator and/or biomarker of GC.

中文翻译：

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Na+/K+-ATP酶α1亚基的表达与胃癌的肿瘤发展和临床结局有关

背景

Na ⁺ /K ⁺ -ATPase alpha1 亚基 (ATP1A1) 是 Na ⁺ /K ⁺ -ATPase (NKA) 的重要组成部分，NKA 是一种膜泵，可维持较低的细胞内 Na ⁺ /K ⁺比率并保持细胞体积和渗透压。ATP1A1 最近与肿瘤行为有关。因此，本研究调查了 ATP1A1 在胃癌 (GC) 患者中的作用。

方法

使用 ATP1A1 siRNA 对人 GC 细胞系进行敲低实验，并检查其对增殖、细胞周期、细胞凋亡和细胞运动的影响。通过微阵列分析进行基因表达谱分析。对来自 192 名接受胃切除术的 GC 患者的原发性肿瘤样本进行免疫组织化学分析。

结果

在 NUGC4 和 MKN74 细胞中观察到高 ATP1A1 表达水平。siRNA 诱导的 ATP1A1 敲低可抑制细胞增殖并诱导细胞凋亡。微阵列分析表明，ATP1A1 的敲低导致参与干扰素 (IFN) 信号通路的基因表达上调，例如 STAT1、STAT2、IRF1 和 IRF9。此外，ATP1A1 的消耗改变了 MAPK 通路的磷酸化。免疫组化分析显示ATP1A1的表达与组织学类型、静脉侵犯和病理T分期有关。此外，预后分析显示高 ATP1A1 表达水平与术后生存率差之间存在相关性。

结论

ATP1A1 似乎通过改变 IFN 信号来调节肿瘤进展，而高 ATP1A1 表达水平与 GC 患者术后生存率差有关。目前的结果为 ATP1A1 作为 GC 的介质和/或生物标志物的功能提供了新的见解。