期刊
ONCOTARGET
卷 8, 期 13, 页码 21461-21471出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.15591
关键词
miR-106b-5p; stemness; wnt signalling; tumorigenesis; renal cell carcinoma
资金
- National Key Research and Development Program of China [2016YFC0902600]
- National Natural Science Foundation of China [81572905, 81372730, 81372357]
- Guangdong Provincial Science and Technology Foundation [2014B020212015]
- Guangzhou Science and Technology Foundation [201504281732585, 201607010238]
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/beta-catenin signalling. miR-106p-5p overexpression simultaneously targets multiple negative regulators of the Wnt/beta-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/beta-catenin signalling, likely serving as a potential therapeutic target for ccRCC.
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