| The stability of mRNA transcripts is critical to the regulation of gene expression, and is controlled through specific protein binding to AU rich elements (AREs) in the 3'UTR of target mRNAs. We hypothesized that the mRNA-binding protein HuR regulates the stability of IL-8, and that IGF-1 mediates this stability regulation in ovarian cancer cells. We found that IGF-1 induced HuR and IL-8, where high IL-8 expression correlated with high HuR levels. Endogenous IL-8 mRNA decay was very rapid, however following IGF-1 stimulation IL-8 mRNA half-life was stabilized. Transfection with HuR stabilized IL-8 mRNA, and HuR was found to bind to the IL-8 3'UTR in ovarian cancer cells. Reporter constructs of the IL-8 3'UTR containing mutated AREs demonstrated a decreased rate of decay as compared to wildtype constructs. Our results suggest that IGF-mediated increases in IL-8 expression in ovarian cancer cells are directly correlated with HuR accumulation which stabilizes IL-8 mRNA. |
