miR-106b-5p promotes renal cell carcinoma aggressiveness and stem-cell-like phenotype by activating Wnt/β-catenin signalling.
miR-106b-5p promotes renal cell carcinoma aggressiveness and stem-cell-like phenotype by activating Wnt/β-catenin signalling.
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miR-106b-5p通过激活Wnt/β-catenin信号传导促进肾细胞癌侵袭性和干细胞样表型
DOI：
10.18632/oncotarget.15591
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发表时间：
2017-03-28
期刊：
影响因子：
--
通讯作者：
Luo JH
中科院分区：
文献类型：
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作者：
Lu J;Wei JH;Feng ZH;Chen ZH;Wang YQ;Huang Y;Fang Y;Liang YP;Cen JJ;Pan YH;Liao B;Chen WF;Chen W;Luo JH
探讨miR-106b-5p在调节肾透明细胞癌(CcRCC)肿瘤干细胞样表型中的作用。实时荧光定量聚合酶链式反应(Real-Time-PCR)检测肾癌细胞株和患者标本中miR-106b-5p的表达水平。在体内和体外进行了一系列检测，以证实miR-106b-5p对ccRCC茎表型的影响。CcRCC细胞和组织中miR-106b-5p的表达高于正常对照组。功能获得和功能丧失研究表明，miR-106b-5p在ccRCC细胞中的过表达增加了球体的形成能力和侧群细胞的比例。通过原位肾癌模型和尾静脉注射模型，在ccRCC细胞中异位表达miR-106b-5p分别增加了肿瘤的生长速度和肺内转移集落的数量。机制研究表明，miR-106b-5p对Wnt/β-catenin信号转导有激活作用。MIR-106p-5p的过表达同时靶向Wnt/β-catenin途径的多个负调控因子，即LZTFl1、SFRP1和DKK2。此外，我们还证实miR-106b-5p及其靶点的表达与TCGA患者的总体生存有关。这些发现表明，miR-106b-5p介导了Wnt/β-catenin信号的结构性激活，可能成为ccRCC的潜在治疗靶点。
To examine the role of miR-106b-5p in regulating the cancer stem-cell-like phenotype in clear cell renal cell carcinomas (ccRCC). 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. 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. 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.