miR-211-5p Suppresses Metastatic Behavior by Targeting SNAI1 in Renal Cancer
miR-211-5p Suppresses Metastatic Behavior by Targeting SNAI1 in Renal Cancer
复制标题
miR-211-5p 通过靶向 SNAI1 抑制肾癌的转移行为
DOI：
10.1158/1541-7786.mcr-16-0288
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发表时间：
2017-04-01
影响因子：
5.2
通讯作者：
Chen, Xiaonan
中科院分区：
文献类型：
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作者：
Wang, Kefeng;Jin, Wei;Chen, Xiaonan
已知Snail家族转录抑制因子1（SNAI 1）促进肾细胞癌（RCC）的转移表型。然而，SNAI 1促进RCC转移的机制在很大程度上尚未探索。生物信息学和定量验证显示，与非转移性RCC组织相比，转移性RCC临床标本中miR-211- 5 p下调。miR-211- 5 p过表达通过下调SNAI 1表达抑制RCC细胞迁移和侵袭。荧光素酶报告基因检测表明miR-211- 5 p直接靶向SNAI 1的3′-UTR。此外，miR-211- 5 p降低异种移植肿瘤重量并减少小鼠体内肿瘤转移。这些发现表明，miR-211- 5 p介导的SNAIL 1表达抑制有助于抑制RCC进展。结论：靶向miR-211- 5 p/SNAI 1信号通路可能成为治疗肾癌转移的新途径。Mol Cancer Res; 15（4）; 448-56.©2017 AACR.
The Snail family transcriptional repressor 1 (SNAI1) is known to promote metastatic phenotypes in renal cell carcinoma (RCC). However, the mechanism by which SNAI1 promotes RCC metastasis remains largely unexplored. Here, bioinformatics and quantitative validation revealed that miR-211-5p was downregulated in metastatic RCC clinical specimens compared with nonmetastatic RCC tissues. Overexpression of miR-211-5p suppressed RCC cell migration and invasion via downregulation of SNAI1 expression. Luciferase reporter assays demonstrated that miR-211-5p directly targeted 3′-UTR of SNAI1. Furthermore, miR-211-5p decreased xenograft tumor weight and reduced in vivo tumor metastasis in mice. These findings indicate that miR-211-5p-mediated inhibition of SNAIL1 expression contributes to the suppression of RCC progression. Implications: Targeting the miR-211-5p/SNAI1 signaling pathway may be a novel therapeutic approach for the treatment of RCC metastasis. Mol Cancer Res; 15(4); 448–56. ©2017 AACR.