Tumor‐suppressive microRNA‐1291 directly regulates glucose transporter 1 in renal cell carcinoma

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