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Updated: May 9, 2026

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
Tumor-suppressive microRNA-1291 directly regulates glucose transporter 1 in renal cell carcinoma
Takeshi Yamasaki1, Naohiko Seki, Hirofumi Yoshino
1Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Abstract:
Our recent studies of microRNA (miRNA) expression signatures demonstrated that microRNA-1291 (miR-1291) was significantly downregulated in renal cell carcinoma (RCC) clinical specimens and was a putative tumor-suppressive miRNA in RCC. The aim of the present study was to investigate the functional significance of miR-1291 in cancer cells and to identify novel miR-1291-mediated cancer pathways and target genes in RCC. Expression of miR-1291 was significantly downregulated in RCC tissues compared with adjacent non-cancerous tissues. Restoration of mature miR-1291 in RCC cell lines (A498 and 786-O) revealed significant inhibition of cell proliferation, migration and invasion, suggesting that miR-1291 functioned as a tumor suppressor. To identify miR-1291-mediated molecular pathways and targets, we used gene expression analysis (expression of RCC clinical specimens and miR-1291-transfected A498 cells) and in silico database analysis. Our data demonstrated that 79 signaling pathways were significantly regulated by tumor-suppressive miR-1291 in RCC cells. Moreover, solute career family 2 member 1 (SLC2A1) was a candidate target of miR-1291 regulation. The SLC2A1 gene provides instructions for producing glucose transporter protein type 1 (GLUT1). Luciferase reporter assays showed that miR-1291 directly regulated SLC2A1/GLUT1. In RCC clinical specimens, the expression of SLC2A1/GLUT1 mRNA was significantly higher in cancer tissues than in non-cancerous tissues. A significant inverse correlation was recognized between SLC2A1/GLUT1 and miR-1291 expression (r = -0.55, P < 0.0001). Loss of tumor-suppressive miR-1291 enhanced RCC cell proliferation, migration and invasion through targeting SLC2A1/GLUT1. The identification of novel tumor-suppressive miR-1291-mediated molecular pathways and targets has provided new insights into RCC oncogenesis and metastasis.
Insights
MicroRNA-1291 (miR-1291) acts as a tumor suppressor in renal cell carcinoma (RCC). Its downregulation promotes RCC cell proliferation and metastasis by targeting SLC2A1/GLUT1, offering new therapeutic insights.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA-1291 (miR-1291) is downregulated in renal cell carcinoma (RCC).
- miR-1291 is a putative tumor-suppressive miRNA in RCC.
- The functional role and molecular targets of miR-1291 in RCC remain to be fully elucidated.
Purpose of the Study:
- To investigate the functional significance of miR-1291 in RCC.
- To identify novel miR-1291-mediated cancer pathways and target genes in RCC.
Main Methods:
- Gene expression analysis of RCC clinical specimens and miR-1291-transfected cells.
- In silico database analysis.
- Luciferase reporter assays to confirm direct target regulation.
Main Results:
- miR-1291 restoration inhibited RCC cell proliferation, migration, and invasion.
- 79 signaling pathways were significantly regulated by miR-1291.
- Solute carrier family 2 member 1 (SLC2A1), encoding glucose transporter protein type 1 (GLUT1), was identified as a direct target of miR-1291.
- SLC2A1/GLUT1 expression was inversely correlated with miR-1291 levels in RCC tissues.
Conclusions:
- miR-1291 functions as a tumor suppressor in RCC.
- The miR-1291/SLC2A1/GLUT1 axis plays a critical role in RCC oncogenesis and metastasis.
- Targeting this pathway may offer novel therapeutic strategies for RCC.
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