Abstract
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.
Highlights
Renal cell carcinoma (RCC) originates from renal tubular epithelial cell and accounts for approximately 3% of adult malignancies [1]
Snai1 family transcriptional repressor 1 (SNAI1) promotes RCC cell migration and invasion Previous studies indicated that SNAI1 could function as an oncogene in RCC [21,22,23], but the detailed mechanisms remained unclear
G, The expression of SNAI1 in RCC patients according to the tumor pathological stage
Summary
Renal cell carcinoma (RCC) originates from renal tubular epithelial cell and accounts for approximately 3% of adult malignancies [1]. More than sixty thousand new cases of RCC were diagnosed in recent years in the United States, resulting in about ten thousand deaths [2,3,4]. It is necessary to investigate the mechanisms of RCC progression and identify highly specific carcinoma-associated markers for finding new strategies for early diagnosis and treatment of RCC. Recent studies have found that SNAI1 promotes tumor progression in gastric cancer [8], pancreatic cancer [9], colorectal cancer [10], lung cancer [11], and RCC [12,13,14]
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