Sweet-P inhibition of glucocorticoid receptor β as a potential cancer therapy

Abstract

The need for the development of new cancer therapies and push for the design of new targeting techniques is on the rise, and would be useful for cancers that are resistant to current drug treatments. The understanding of the genome has significantly advanced cancer therapy, as well as prevention and earlier detection. This research highlight discusses a potential new type of cancer-targeting molecule, Sweet-P, which is the first of its kind. Sweet-P specifically targets the microRNA-144 binding site in the 3' untranslated region (3' UTR) of the human glucocorticoid receptor β (GRβ), which has been demonstrated to increase expression. GRβ has been shown to be highly expressed in cells from solid tumors of uroepithelial carcinomas, gliomas, osteosarcomas, and hepatocellular carcinomas, as well as in liquid tumor cells from leukemia patients. In non-cancerous diseases, GRβ has been shown to be highly expressed in glucocorticoid-resistant asthma. These maladies brought the need for the development of the Sweet-P anti-GRβ molecule. Sweet-P was shown to repress the migration of bladder cancer cells, and may serve as a new therapeutic for GRβ-related diseases.

Keywords: GR; GR alpha; GR beta; Glucocorticoid receptor; Sweet-P; asthma; bladder cancer; cancer; glucocorticoids; growth; miRNA; microRNA; migration.

Figure 1. Sweet-P inhibition of GRβ reduces signaling that leads to cancer

Sweet-P inhibits miR144 binding to the 3′UTR of human GRβ, resulting in reduced expression. Sweet-P inhibition of GRβ increases GRα and PTEN activity and decreases AKT, which leads to reduced cancer growth and migration.