MiR‐16 a novel regulator of the insulin dependent glucose transporter, GLUT‐4

MicroRNAs are small noncoding RNAs of approximately 22 nucleotides that negatively regulate translation of the target messenger RNA (mRNA) and therefore have cellular functions. microRNA‐16 (miR‐16) is known to display anti‐proliferative effects. We observed that miR‐16 was upregulated in non‐proliferative human senescent endothelial cells. Computational analysis of the potential binding sites of miR‐16 predicted that GLUT‐4, an insulin‐dependent glucose transporter, is a potential target of miR‐16. We therefore tested the hypothesis that miR‐16 downregulates cellular glucose metabolism. In HUVEC, inhibition of endogenous miR‐16 up‐regulated GLUT‐4 protein levels by 1.7 fold (p=0.0037 n=9). Using a GLUT‐4 luciferase reporter gene assay, miR‐16 decreased luciferase activity by 6.5 ± 0.6 (p<0.0001) folds demonstrating direct regulation of miR‐16 on the 3′UTR of the GLUT‐4. Finally, in mice fed a regular or high fat diet, skeletal muscle expression of GLUT‐4 tended to negatively correlate with miR‐16 levels (p=0.0998, r2=0.3866). These results suggest that miR‐16 is a direct negative regulator of GLUT‐4 and may be involved in the regulation of metabolism. Supported by CIHR MOP14496