Downregulation of microRNA-182-5p contributes to renal cell carcinoma proliferation via activating the AKT/FOXO3a signaling pathway

Molecular Cancer

Research

Zhenghui Hu¹  Xin Xu¹  Liping Xie¹  Xiao Wang¹  Jindan Luo¹  Shiqi Li¹  Yeqing Mao¹  Ben Liu¹  Xianglai Xu¹  Zhen Liang¹  Hong Chen¹  Jian Wu¹  Yi Zhu¹  Xiangyi Zheng¹  Yiwei Lin¹ 

[1] Department of Urology, First Affiliated Hospital, School of Medicine, Zhejiang University, Qingchun Road 79, 310003, Hangzhou, Zhejiang Province, China;

关键词: Renal cell carcinoma;    Proliferation;    Microrna-182-5p;    FLOT1;   

DOI  :  10.1186/1476-4598-13-109

 received in 2013-11-03, accepted in 2014-05-12,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundEmerging evidence has suggested that dysregulation of miR-182-5p may contribute to tumor development and progression in several types of human cancers. However, its role in renal cell carcinoma (RCC) is still unknown.MethodsQuantitative RT-PCR was used to quantify miR-182-5p expression in RCC clinical tissues. Bisulfite sequencing PCR was used for DNA methylation analysis. The CCK-8, colony formation, flow cytometry, and a xenograft model were performed. Immunohistochemistry was conducted using the peroxidase and DAB methods. A miR-182-5p target was determined by luciferase reporter assays, quantitative RT-PCR, and Western blotting.ResultsmiR-182-5p is frequently down-regulated in human RCC tissues. Epigenetic modulation may be involved in the regulation of miR-182-5p expression. Enforced expression of miR-182-5p in RCC cells significantly inhibited the proliferation and tumorigenicity in vitro and in vivo. Additionally, overexpression of miR-182-5p induced G1-phase arrest via inhibition of AKT/FOXO3a signaling. Moreover, FLOT1 was confirmed as a target of miR-182-5p. Silencing FLOT1 by small interfering RNAs phenocopied the effects of miR-182-5p overexpression, whereas restoration of FLOT1 in miR-182-5p -overexpressed RCC cells partly reversed the suppressive effects of miR-182-5p.ConclusionsThese findings highlight an important role for miR-182-5p in the pathogenesis of RCC, and restoration of miR-182-5p could be considered as a potential therapeutic strategy for RCC therapy.

【 授权许可】

Unknown   
© Xu 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.