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ABSTRACT: Purpose
To examine the role of miR-106b-5p in regulating the cancer stem-cell-like phenotype in clear cell renal cell carcinomas (ccRCC).Experimental design
Real-time PCR was performed to evaluate miR-106b-5p levels in ccRCC cell lines and patients specimens. A series of in vivo and in vitro assays were performed to confirm the effect of miR-106b-5p on ccRCC stemness phenotype.Results
ccRCC cells and tissues expressed more miR-106b-5p than normal controls. Gain- and loss-of-function studies demonstrated that overexpression of miR-106b-5p in ccRCC cells increased the spheres formation ability and the proportion of side population cells. Ectopic expression of miR-106b-5p in ccRCC cells increased tumour growth rates and the number of metastatic colonies in the lungs by using an orthotopic kidney cancer model and a tail vein injection model, respectively. Mechanistic studies revealed that, miR-106b-5p has an activating effect on Wnt/?-catenin signalling. miR-106p-5p overexpression simultaneously targets multiple negative regulators of the Wnt/?-catenin pathway, namely, LZTFL1, SFRP1 and DKK2. In addition, we also confirmed that miR-106b-5p and its targets expression correlates with the overall-survival of ccRCC patients from TCGA.Conclusions
These findings suggest that miR-106b-5p mediates the constitutive activation of Wnt/?-catenin signalling, likely serving as a potential therapeutic target for ccRCC.
SUBMITTER: Lu J
PROVIDER: S-EPMC5400598 | biostudies-literature | 2017 Mar
REPOSITORIES: biostudies-literature
Lu Jun J Wei Jin-Huan JH Feng Zi-Hao ZH Chen Zhen-Hua ZH Wang Yong-Qian YQ Huang Yong Y Fang Yong Y Liang Yan-Ping YP Cen Jun-Jie JJ Pan Yi-Hui YH Liao Bing B Chen Wen-Fang WF Chen Wei W Luo Jun-Hang JH
Oncotarget 20170301 13
<h4>Purpose</h4>To examine the role of miR-106b-5p in regulating the cancer stem-cell-like phenotype in clear cell renal cell carcinomas (ccRCC).<h4>Experimental design</h4>Real-time PCR was performed to evaluate miR-106b-5p levels in ccRCC cell lines and patients specimens. A series of in vivo and in vitro assays were performed to confirm the effect of miR-106b-5p on ccRCC stemness phenotype.<h4>Results</h4>ccRCC cells and tissues expressed more miR-106b-5p than normal controls. Gain- and loss- ...[more]