Fig. 6.

Time- and concentration-dependent luciferase activity in response to hydroxyurea treatment of anti-miR-26b transfected K562 cells. Inhibition of miR-26b results in a significant (p < 0.02) increase in luciferase activity and a sigmoidal pattern of action during a time course with HU treatment, with the highest luciferase activity observed after 12 h of treatment (a). A concentration gradient of anti-miR-26b demonstrates an inverse relationship between anti-miR26b concentration and MYB-3′-UTR luciferase activity. This unequivocally demonstrates interaction between miR-26b and the 3′-UTR of MYB (b). The likely implication of this result is that the miR-26b-induced translational inhibition of MYB (a known activator of KLF-1) could result in down-regulation of KLF-1, which is known to directly induce BCL11A expression. In sum, miR-26b could explain the observed up-regulation of γ-globin via a MYB/KLF-1/BCL11A pathway. * Significant difference, p < 0.05