Background

Chemotherapy is, next to surgery and radiotherapy, the mainstay regimen for the clinical management of gastric cancer. This therapy is, however, heavily compromised by the acquisition of resistance. Here, we aimed to clarify the potential involvement of long non-coding RNA SNGH3 in the acquisition of cisplatin resistance and stemness in gastric cancer.

Methods

Cell viability and proliferation were measured using Cell Counting Kit-8 and colony formation assays, respectively. Stem cell-like cell growth was evaluated using a mammosphere formation assay. RNA levels of SNHG2, OCT-4, SOX-2, CD44, miR-3619-5p and ARL2 were determined using qRT-PCR, whereas protein levels of OCT-4, SOX-2, CD44, ARL2, STAT3 and pSTAT3 were determined using Western blotting. Dual luciferase reporter assays were employed to interrogate regulatory interactions between STAT3, SNHG3, miR-3619-5p and ARL2, respectively. Direct binding of STAT3 to the SNHG3 promoter was investigated using a chromatin immunoprecipitation assay.

Results

We found that IL-6 triggered stem cell-like properties in cisplatin-treated gastric cancer cells and activated STAT3, which in turn transcriptionally regulated SNHG3 expression. SNHG3 expression up-regulation positively correlated with cisplatin resistance and stemness of gastric cancer cells, while SNHG3 down-regulation inhibited stem cell-like properties. In addition, we found that SNHG3 up-regulated ARL2 expression through sponging miR-3619-5p, which predominantly mediated the oncogenic properties of SNHG3 in this disease.

Conclusions

Our data indicate an involvement of aberrant SNHG3 over-expression in the acquisition of both cisplatin resistance and stemness of gastric cancer cells, and of the IL-6/STAT3/SNHG3/miR-3619-5p/ARL2 signaling cascade in the oncogenic properties of SNHG3.

中文翻译：

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由 IL-6/STAT3 反式激活诱导的长链非编码 RNA SNHG3 通过调节 miR-3619-5p/ARL2 轴促进胃癌细胞的干细胞样特性。

背景

化疗是继手术和放疗之后胃癌临床治疗的主要方案。然而，这种疗法因获得抗性而严重受损。在这里，我们旨在阐明长链非编码 RNA SNGH3 在胃癌中获得顺铂耐药性和干性的潜在参与。

方法

分别使用 Cell Counting Kit-8 和集落形成测定法测量细胞活力和增殖。使用乳腺球形成测定法评估干细胞样细胞生长。使用 qRT-PCR 测定 SNHG2、OCT-4、SOX-2、CD44、miR-3619-5p 和 ARL2 的 RNA 水平，而测定 OCT-4、SOX-2、CD44、ARL2、STAT3 和 pSTAT3 的蛋白质水平使用蛋白质印迹法。双荧光素酶报告基因检测分别用于询问 STAT3、SNHG3、miR-3619-5p 和 ARL2 之间的调节相互作用。使用染色质免疫沉淀测定研究了 STAT3 与 SNHG3 启动子的直接结合。

结果

我们发现 IL-6 在顺铂处理的胃癌细胞中触发干细胞样特性并激活 STAT3，进而转录调节 SNHG3 的表达。SNHG3表达上调与顺铂耐药和胃癌细胞干性呈正相关，而SNHG3下调抑制干细胞样特性。此外，我们发现 SNHG3 通过海绵化 miR-3619-5p 上调 ARL2 表达，这主要介导了 SNHG3 在这种疾病中的致癌特性。

结论

我们的数据表明异常 SNHG3 过表达参与了胃癌细胞顺铂耐药性和干性的获得，以及 IL-6/STAT3/SNHG3/miR-3619-5p/ARL2 信号级联在胃癌的致癌特性中的作用。 SNHG3。