Control the intracellular NF-κB activity by a sensor consisting of miRNA and decoy

Many diseases are associated with the abnormal activation of NF-kappa B and its signaling pathway. NF-kappa B has become an important target for disease treatment and development of new drugs. Many various NF-kappa B inhibitors were therefore developed; however, they have difficulties to become clinical drugs due to their adverse side effects resulted from the affected normal physiological functions of this transcription factor. To overcome this limitation, this study construct a transgenic vector that can express an artificial miRNA targeting NF-kappa B RelA under the control of a NF-kappa B-specific promoter. The promoter consists of a NF-kappa B decoy and a minimal promoter. The vector was named as decoy minimal promoter-artificial microRNA (DMP-amiRNA). This study verified that this vector can sense and control the intracellular NF-kappa B activity upon transfection. Working of the vector forms a perfect feedback loop that realizes the NF-kappa B self-control. With the vector in cells, the higher NF-kappa B activity, the higher DMP transcriptional activity, and the more amiR533 expression. DMP-amiRNA can moderately inhibit the intracellular NF-kappa B activity but exert no significant effect on cell viability. This study therefore develops a new strategy for inhibiting over activity of NF-kappa B, which should has great potential in clinical application.