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MicroRNA-194 通过靶向 FoxM1 抑制胃癌细胞的上皮-间充质转化。

MicroRNA-194 inhibits the epithelial-mesenchymal transition in gastric cancer cells by targeting FoxM1.

机构信息

Department of Colorectal Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, 312000, Zhejiang, China.

出版信息

Dig Dis Sci. 2014 Sep;59(9):2145-52. doi: 10.1007/s10620-014-3159-6. Epub 2014 Apr 19.

Abstract

AIM

We hypothesized that miR-194 may control Forkhead box protein M1 (FoxM1) expression in gastric cancer cells and therefore may have therapeutic potential in gastric cancer.

METHODS

The expression level of miR-194 was examined using real-time PCR in human gastric cancer and noncancerous gastric tissues, gastric cancer cell and normal gastric mucosal epithelial cell. We examined whether the miR-194 regulates cell migration and invasion, and the epithelial-mesenchymal transition Phenotype by inhibiting FoxM1 in gastric cancer cells.

RESULTS

The expression of miR-194 was significantly lower in gastric cancer compared with non-cancerous gastric tissues and cells. Exogenous expression of miR-194 inhibited cell migration, invasion, and the epithelial-mesenchymal transition phenotype in gastric cancer cells. Moreover, we discovered a novel post-transcriptional regulatory mechanism of FoxM1 expression that is mediated by miR-194.

CONCLUSION

Our study clearly demonstrates that miR-194 inhibits the acquisition of the EMT phenotype in gastric cancer cells by downregulating FoxM1, thereby inhibiting cell migration and invasion during cancer progression.

摘要

目的

我们假设 miR-194 可能控制胃癌细胞中的叉头框蛋白 M1(FoxM1)表达,因此在胃癌中可能具有治疗潜力。

方法

使用实时 PCR 检测人胃癌和非癌性胃组织、胃癌细胞和正常胃黏膜上皮细胞中 miR-194 的表达水平。我们通过抑制胃癌细胞中的 FoxM1 来检测 miR-194 是否调节细胞迁移和侵袭以及上皮-间充质转化表型。

结果

与非癌性胃组织和细胞相比,胃癌中 miR-194 的表达明显降低。外源性表达 miR-194 抑制了胃癌细胞的迁移、侵袭和上皮-间充质转化表型。此外,我们发现了一种由 miR-194 介导的 FoxM1 表达的新型转录后调控机制。

结论

我们的研究清楚地表明,miR-194 通过下调 FoxM1 抑制胃癌细胞中 EMT 表型的获得,从而抑制癌症进展过程中的细胞迁移和侵袭。

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