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微小RNA-19a通过PI3K/AKT信号通路促进胃癌上皮-间质转化

MiR-19a promotes epithelial-mesenchymal transition through PI3K/AKT pathway in gastric cancer.

作者信息

Lu Wei-Dong, Zuo Yun, Xu Zhen, Zhang Min

机构信息

Wei-Dong Lu, Yun Zuo, Zhen Xu, Min Zhang, Department of Oncology, Zhangjiagang First People's Hospital, Suzhou University, Zhangjiagang 215600, Jiangsu Province, China.

出版信息

World J Gastroenterol. 2015 Apr 21;21(15):4564-73. doi: 10.3748/wjg.v21.i15.4564.

Abstract

AIM

To investigate the mechanism by which miR-19a is up-regulated in gastric cancer (GC), which plays an oncogenic role.

METHODS

In the present study, we investigated the role of miR-19a in gastric tissues as well as two GC cell lines. In vivo, we detected the basal expression level of miR-19a using real-time reverse transcription-PCR (RT-PCR), and the relevance between expression of miR-19a and clinicopathological information was analyzed. In vitro, miR-19a was ectopically expressed using overexpression and knock-down strategies.

RESULTS

Overexpression of miR-19a was significantly associated with metastasis of GC and inferior overall prognosis. However, no significant correlation was found between miR-19a expression and other characteristics such as age, gender, tobacco, alcohol or tumor size. Cell proliferation, migration and invasion assays showed that overexpression of miR-19a promoted the proliferation, migration and invasion, and that overexpression of miR-19a promoted the epithelial-mesenchymal transition through activating the PI3K/AKT pathway. Blocking the PI3K/AKT pathway could cancel the effect of miR-19a.

CONCLUSION

All together, our results suggest that miR-19a could be used as a promising therapeutic target in the treatment of GC.

摘要

目的

研究在胃癌(GC)中发挥致癌作用的miR-19a上调的机制。

方法

在本研究中,我们研究了miR-19a在胃组织以及两种GC细胞系中的作用。在体内,我们使用实时逆转录聚合酶链反应(RT-PCR)检测miR-19a的基础表达水平,并分析miR-19a表达与临床病理信息之间的相关性。在体外,使用过表达和敲低策略异位表达miR-19a。

结果

miR-19a的过表达与GC转移及总体预后较差显著相关。然而,未发现miR-19a表达与年龄、性别、烟草、酒精或肿瘤大小等其他特征之间存在显著相关性。细胞增殖、迁移和侵袭实验表明,miR-19a的过表达促进了细胞增殖、迁移和侵袭,并且miR-19a的过表达通过激活PI3K/AKT途径促进上皮-间质转化。阻断PI3K/AKT途径可消除miR-19a的作用。

结论

总之,我们的结果表明miR-19a可作为GC治疗中一个有前景的治疗靶点。

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