Oncotarget

Research Papers:

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

Jun Lu, Jin-Huan Wei, Zi-Hao Feng, Zhen-Hua Chen, Yong-Qian Wang, Yong Huang, Yong Fang, Yan-Ping Liang, Jun-Jie Cen, Yi-Hui Pan, Bing Liao, Wen-Fang Chen, Wei Chen and Jun-Hang Luo _

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Oncotarget. 2017; 8:21461-21471. https://doi.org/10.18632/oncotarget.15591

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Abstract

Jun Lu1,*, Jin-Huan Wei1,*, Zi-Hao Feng1,*, Zhen-Hua Chen1,*, Yong-Qian Wang2, Yong Huang1, Yong Fang1, Yan-Ping Liang1, Jun-Jie Cen1, Yi-Hui Pan1, Bing Liao3, Wen-Fang Chen3, Wei Chen1, Jun-Hang Luo1

1Department of Urology, First Affiliated Hospital, Sun Yat-sen University, Guangdong, China

2Department of Musculoskeletal Oncology, First Affiliated Hospital, Sun Yat-sen University, Guangdong, China

3Department of Pathology, First Affiliated Hospital, Sun Yat-sen University, Guangdong, China

*These authors contributed equally to this work

Correspondence to:

Jun-Hang Luo, email: [email protected]

Keywords: miR-106b-5p, stemness, Wnt signalling, tumorigenesis, renal cell carcinoma

Received: October 29, 2016     Accepted: February 06, 2017     Published: February 21, 2017

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/β-catenin signalling. miR-106p-5p overexpression simultaneously targets multiple negative regulators of the Wnt/β-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/β-catenin signalling, likely serving as a potential therapeutic target for ccRCC.


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