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微小RNA-335通过靶向锌指E盒结合蛋白2抑制结直肠癌的侵袭和转移。

MicroRNA-335 inhibits invasion and metastasis of colorectal cancer by targeting ZEB2.

作者信息

Sun ZhiFeng, Zhang Zhang, Liu Zidong, Qiu Bo, Liu Kan, Dong Guanglong

机构信息

Department of Gastrointestinal Surgery, Xi Jing Digestive Hospital, Fourth Military Medical University, Xi'an, Shan Xi Province, China.

出版信息

Med Oncol. 2014 Jun;31(6):982. doi: 10.1007/s12032-014-0982-8. Epub 2014 May 15.

Abstract

MicroRNAs have been suggested to play a vital role in regulate tumor progression and invasion. However, the expression of miR-335 in colorectal cancer (CRC) and its clinical significance are not known. Here, we report that miR-335 is a tumor suppressor by regulating expression of ZEB2. In this study, we showed that downregulated miR-335 levels in highly invasive CRC cell lines and tissues. Kaplan-Meier survival analysis indicated that patients with reduced miR-335 had a poor overall survival. Furthermore, enhancing the expression of miR-335 inhibited CRC cell migration and invasion in vitro and lung and liver metastasis in vivo, while silencing its expression resulted in increased migration and invasion. Additionally, we identified a novel miR-335 target, ZEB2, and the direct interaction between them was verified by 3'-untranslated region dual-luciferase reporter assay. In conclusion, our results demonstrate that miR-335 functions as a tumor suppressor and play a role in inhibiting metastasis of CRC cells through targeting ZEB2. These findings suggest that miR-335 may be useful as a new potential therapeutic target for CRC.

摘要

微小RNA被认为在调节肿瘤进展和侵袭中起着至关重要的作用。然而,miR-335在结直肠癌(CRC)中的表达及其临床意义尚不清楚。在此,我们报告miR-335通过调节ZEB2的表达发挥肿瘤抑制作用。在本研究中,我们发现高侵袭性CRC细胞系和组织中miR-335水平下调。Kaplan-Meier生存分析表明,miR-335降低的患者总生存期较差。此外,增强miR-335的表达可在体外抑制CRC细胞迁移和侵袭,并在体内抑制肺和肝转移,而沉默其表达则导致迁移和侵袭增加。此外,我们鉴定了一个新的miR-335靶标ZEB2,并通过3'-非翻译区双荧光素酶报告基因检测验证了它们之间的直接相互作用。总之,我们的结果表明miR-335作为一种肿瘤抑制因子,通过靶向ZEB2在抑制CRC细胞转移中发挥作用。这些发现提示miR-335可能作为CRC的一种新的潜在治疗靶点。

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