MicroRNA-181a promotes tumor growth and liver metastasis in colorectal cancer by targeting the tumor suppressor WIF-1

Molecular Cancer

Research

Jianzhong Xi¹  Zhiqian Zhang²  Zhiguo Chen³  Tiancheng Zhan³  Dengbo Ji³  Jin Gu³  Li Yan³  Yunfeng Yao³  Ming Li³ 

[1] Department of Biomedical Engineering, College of Engineering, Peking University, 100871, Beijing, China;Department of Cell Biology, Peking University Cancer Hospital & Institute, No. 52 Fucheng Rd., 100142, Haidian District, Beijing, China;Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Colorectal Surgery, Peking University Cancer Hospital & Institute, No. 52 Fucheng Rd., 100142, Haidian District, Beijing, China;

关键词: miR-181a;    Colorectal cancer;    Liver metastasis;    WIF-1;   

DOI  :  10.1186/1476-4598-13-86

 received in 2014-01-16, accepted in 2014-04-15,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundGiven the emerging role of microRNA in tumor disease progression, we investigated the association between microRNA expression, liver metastasis and prognosis of colorectal cancer.MethodsColorectal cancer tissues from patients with or without liver metastases were profiled to identify differentially expressed microRNA. Expression profile was further assessed using quantitative reverse transcription PCR and in situ hybridization. Correlation between miR-181a expression, the most differentially expressed microRNA, between patients with and without liver metastasis, and its downstream target genes were investigated using qRT-PCR. Luciferase reporter assay was conducted to establish functional association between miR-181a and its target genes. Manipulation of miR-181a expression and its consequences in tumor growth and metastasis were demonstrated in various in vitro and in vivo models.ResultsmiR-181a was revealed being the most elevated in CRC with liver metastases. miR-181a expression correlated with advanced stage, distant metastasis, and served as an independent prognostic factor of poor overall survival. Stable transfection of CRC cell lines with miR-181a promoted cell motility and invasion, as well as tumor growth and liver metastasis,while silencing its expression resulted in reduced migration and invasion. Additionally, we identified WIF-1 as direct and functional targets of miR-181a. Ectopic expression of miR-181a suppressed the epithelial markers E-cadherin and β-catenin, while enhanced the mesenchymal markers vimentin.ConclusionOur data demonstrate that miR-181a expression is associated with CRC liver metastasis and survival. miR-181a has strong tumor-promoting effects through inhibiting the expression of WIF-1, and its potential role in promoting epithelial-mesenchymal transition.

【 授权许可】

Unknown   
© Ji et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.