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微小RNA-506通过直接靶向癌基因EZH2抑制结肠癌的肿瘤增殖和转移。

MicroRNA-506 suppresses tumor proliferation and metastasis in colon cancer by directly targeting the oncogene EZH2.

作者信息

Zhang Yi, Lin Changwei, Liao Guoqing, Liu Sheng, Ding Jie, Tang Fang, Wang Zhenran, Liang Xingsi, Li Bo, Wei Yangchao, Huang Qi, Li Xuan, Tang Bo

机构信息

Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, 410008, PR China.

Department of Oncological Surgery, Affiliated Hospital of Xuzhou Medical College, 221000, PR China.

出版信息

Oncotarget. 2015 Oct 20;6(32):32586-601. doi: 10.18632/oncotarget.5309.

Abstract

Increasing evidence reveals that aberrant expression of microRNA contributes to the development and progression of colon cancer, but the roles of microRNA-506 (miR-506) in colon cancer remain elusive. Here, we demonstrated that miR-506 was down-regulated in colon cancer tissue and cells and that miR-506 expression was inversely correlated with EZH2 expression, tumor size, lymph node invasion, TNM stage and metastasis. A high level of miR-506 identified patients with a favorable prognosis. In vitro and in vivo experiments confirmed that miR-506 inhibits the proliferation and metastasis of colon cancer, and a luciferase reporter assay confirmed that EZH2 is a direct and functional target of miR-506 via the 3'UTR of EZH2. The restoration of EZH2 expression partially reversed the proliferation and invasion of miR-506-overexpressing colon cancer cells. Moreover, we confirmed that the miR-506-EZH2 axis inhibits proliferation and metastasis by activating/suppressing specific downstream tumor-associated genes and the Wnt/β-catenin signaling pathway. Taking together, our study sheds light on the role of miR-506 as a suppressor for tumor growth and metastasis and raises the intriguing possibility that miR-506 may serve as a new potential marker for monitoring and treating colon cancer.

摘要

越来越多的证据表明,微小RNA的异常表达促进了结肠癌的发生和发展,但微小RNA-506(miR-506)在结肠癌中的作用仍不清楚。在此,我们证明miR-506在结肠癌组织和细胞中表达下调,且miR-506表达与EZH2表达、肿瘤大小、淋巴结浸润、TNM分期及转移呈负相关。高水平的miR-506提示患者预后良好。体外和体内实验证实miR-506抑制结肠癌的增殖和转移,荧光素酶报告基因检测证实EZH2是miR-506通过EZH2的3'非翻译区的直接功能性靶点。EZH2表达的恢复部分逆转了miR-506过表达的结肠癌细胞的增殖和侵袭。此外,我们证实miR-506-EZH2轴通过激活/抑制特定的下游肿瘤相关基因和Wnt/β-连环蛋白信号通路来抑制增殖和转移。综上所述,我们的研究揭示了miR-506作为肿瘤生长和转移抑制因子的作用,并提出了miR-506可能作为监测和治疗结肠癌的新的潜在标志物的有趣可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66b7/4741714/11fbc8ac548d/oncotarget-06-32586-g001.jpg

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