GLI family zinc finger 1 mRNA 3'-untranslated region (GLI1 mRNA 3'-UTR) (GLI1 mRNA 3'-UTR)

The GLI family zinc finger 1 (GLI1) mRNA 3'-untranslated region (3'-UTR) is a critical regulatory sequence located at the 3' end of the GLI1 transcript, which encodes the primary transcriptional activator of the Hedgehog (Hh) signaling pathway (UniProt P08151). This region serves as a scaffold for various microRNAs, such as miR-324-5p and miR-133b, and RNA-binding proteins that modulate the stability and translation of the mRNA (Ferretti et al., 2008, Nature Genetics). In many cancers, including medulloblastoma and basal cell carcinoma, the GLI1 3'-UTR is involved in the dysregulation of Hh signaling, often through the loss of microRNA-mediated suppression, leading to overexpression of the GLI1 protein and subsequent tumor growth (PubMed: 18469814). As a therapeutic target, the GLI1 mRNA is targeted by RNA-based therapies such as the antisense oligonucleotide ISIS 183750 (IONIS-GLI1Rx), which was developed to reduce GLI1 levels by inducing mRNA degradation. These approaches are particularly valuable for treating tumors that have developed resistance to upstream Hh pathway inhibitors like vismodegib, which target the Smoothened (SMO) receptor. By directly targeting the mRNA of the terminal effector, these strategies provide a more direct method of pathway inhibition in GLI-dependent malignancies.

Other names

GLI1 3'-UTRGLI1 3' untranslated regionGLI1 mRNA 3' UTRGLI family zinc finger 1 3'-UTR

Antisense-mediated degradation of GLI1 mRNA via RNase H recruitment or RNA interference (RNAi) to suppress GLI1 protein synthesis.