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MiR-106b-5p promotes renal cell carcinoma aggressiveness and stem-cell-like phenotype by activating Wnt/?-catenin signalling.


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

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Publications

miR-106b-5p promotes renal cell carcinoma aggressiveness and stem-cell-like phenotype by activating Wnt/β-catenin signalling.

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]

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