Background

Gastric cell carcinoma (GCC) is a common and high-incidence malignant gastrointestinal cancer that seriously threatens human life and safety. Evidences suggest that microRNAs (miRNAs) exhibit an essential role in regulating the occurrence and development of GCC, while the effects and possible mechanisms remain to be further explored.

Objective

This study was designed to explore whether miR-200c-3p exerted its functional role in the growth and metastasis of GCC, and investigate the possible mechanisms.

Methods

The expression levels of miR-200c-3p in GCC tissues and cell lines were detected by qRT-PCR analysis. The functional role of miR-200c-3p in the viability, proliferation, migration and invasion of GCC cells were evaluated by CCK-8, EdU, wound healing and Transwell assays. In addition, the candidate targets of miR-200c-3p was predicted and confirmed by dual-luciferase reporter assay. Moreover, the relationship between miR-200c-3p and target (Krüppel like factor 6, KLF6) was assessed by qRT-PCR and western blot assays. Besides, the expression levels of KLF6 in GCC cells were determined by qRT-PCR and western blot assays. Furthermore, the role of KLF6 in the viability, proliferation, migration and invasion of GCC cells mediated with miR-200c-3p mimics was evaluated by CCK-8, EdU, wound healing and Transwell assays.

Results

In the present study, a new tumor promoting function of miR-200c-3p was disclosed in GCC. We found that the expression of miR-200c-3p was obviously increased in clinic GCC tissues and cell lines. In addition, down-regulation of miR-200c-3p suppressed cell viability, proliferation, migration, and invasion in GCC cells. Moreover, KLF6 was verified as a direct target of miR-200c-3p by binding its 3’-UTR. Additionally, KLF6 was remarkably decreased and was negatively associated with the miR-200c-3p expression in GCC cell lines. Furthermore, over-expression of KLF6 retarded the effects of miR-200c-3p on the growth and metastasis of GCC cell lines.

Conclusions

MiR-200c-3p potentially played a tumor-promoting role in the occurrence and development of GCC, which may be achieved by targeting KLF6.

Graphic abstract

中文翻译：

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MiR-200c-3p 通过 KLF6 加重胃癌

背景

胃癌是严重威胁人类生命安全的常见、高发恶性胃肠道肿瘤。有证据表明，microRNAs (miRNAs) 在调节 GCC 的发生和发展中发挥着重要作用，而其作用和可能的机制仍有待进一步探索。

客观的

本研究旨在探讨miR-200c-3p是否在GCC的生长和转移中发挥功能作用，并探讨可能的机制。

方法

通过qRT-PCR分析检测GCC组织和细胞系中miR-200c-3p的表达水平。通过 CCK-8、EdU、伤口愈合和 Transwell 测定评估 miR-200c-3p 在 GCC 细胞的活力、增殖、迁移和侵袭中的功能作用。此外，通过双荧光素酶报告基因分析预测和确认了 miR-200c-3p 的候选靶标。此外，通过 qRT-PCR 和蛋白质印迹分析评估了 miR-200c-3p 和靶标（Krüppel 样因子 6，KLF6）之间的关系。此外，通过 qRT-PCR 和蛋白质印迹测定法测定 GCC 细胞中 KLF6 的表达水平。此外，通过 CCK-8、EdU、伤口愈合和 Transwell 分析评估了 KLF6 在 miR-200c-3p 模拟物介导的 GCC 细胞的活力、增殖、迁移和侵袭中的作用。

结果

在本研究中，在 GCC 中揭示了 miR-200c-3p 的一种新的肿瘤促进功能。我们发现临床GCC组织和细胞系中miR-200c-3p的表达明显增加。此外，miR-200c-3p 的下调抑制了 GCC 细胞中的细胞活力、增殖、迁移和侵袭。此外，通过结合 miR-200c-3p 的 3'-UTR，证实 KLF6 是 miR-200c-3p 的直接靶标。此外，KLF6 显着降低并且与 GCC 细胞系中的 miR-200c-3p 表达呈负相关。此外，KLF6 的过表达延缓了 miR-200c-3p 对 GCC 细胞系生长和转移的影响。

结论

MiR-200c-3p 可能在 GCC 的发生和发展中发挥促肿瘤作用，这可能通过靶向 KLF6 来实现。

图形摘要