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miR-211-5p Suppresses Metastatic Behavior by Targeting SNAI1 in Renal Cancer
Kefeng Wang1, Wei Jin1, Peng Jin1
1Department of Urology, Shengjing Hospital of China Medical University, Shenyang, China.
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.
Insights
MicroRNA-211-5p (miR-211-5p) suppresses renal cell carcinoma (RCC) metastasis by inhibiting SNAI1 expression. Restoring miR-211-5p levels may offer a new treatment strategy for RCC. Keywords: renal cell carcinoma, metastasis, microRNA, SNAI1.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Snail family transcriptional repressor 1 (SNAI1) is implicated in promoting metastatic phenotypes in renal cell carcinoma (RCC).
- The precise mechanisms underlying SNAI1's role in RCC metastasis are not fully understood.
Purpose of the Study:
- To investigate the role of microRNA-211-5p (miR-211-5p) in the regulation of SNAI1 and its impact on renal cell carcinoma (RCC) metastasis.
- To explore the potential of targeting the miR-211-5p/SNAI1 pathway as a therapeutic strategy for RCC.
Main Methods:
- Bioinformatic analysis and quantitative validation to assess miR-211-5p expression in RCC tissues.
- In vitro experiments including cell migration and invasion assays, and luciferase reporter assays to confirm direct targeting of SNAI1 by miR-211-5p.
- In vivo studies using xenograft mouse models to evaluate the effect of miR-211-5p on tumor growth and metastasis.
Main Results:
- miR-211-5p was found to be significantly downregulated in metastatic RCC tissues compared to non-metastatic tissues.
- Overexpression of miR-211-5p suppressed RCC cell migration and invasion by directly downregulating SNAI1 expression.
- miR-211-5p significantly reduced tumor weight and metastasis in vivo in mouse models.
Conclusions:
- miR-211-5p acts as a tumor suppressor in RCC by inhibiting SNAI1 expression and consequently suppressing metastasis.
- The miR-211-5p/SNAI1 signaling pathway represents a promising therapeutic target for managing renal cell carcinoma metastasis.
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