miR-106b-5p promotes renal cell carcinoma aggressiveness and stem-cell-like phenotype by activating Wnt/β-catenin signalling
Metrics: PDF 1801 views | HTML 1884 views | ?
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
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
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.