Suppressor of fused homolog mRNA 3′-untranslated region (SUFU mRNA 3′-UTR)

The Suppressor of fused homolog (SUFU) mRNA 3′-untranslated region (3′-UTR) is a critical regulatory segment of the SUFU transcript, which encodes a primary negative regulator of the Hedgehog (Hh) signaling pathway (UniProt Q9UMX1). The SUFU protein functions by sequestering GLI transcription factors in the cytoplasm, thereby inhibiting the expression of Hh target genes involved in cell proliferation and differentiation (PubMed: 10559945). The 3′-UTR of SUFU mRNA serves as a docking site for various microRNAs (miRNAs) and RNA-binding proteins that modulate mRNA stability and translation efficiency. In several malignancies, such as medulloblastoma and basal cell carcinoma, overexpression of specific miRNAs (e.g., miR-378) targeting the SUFU 3′-UTR leads to reduced SUFU protein levels, resulting in aberrant Hh pathway activation and tumor growth (PubMed: 25659581). Consequently, the SUFU mRNA 3′-UTR is an emerging therapeutic target for RNA-based interventions, including antisense oligonucleotides and miRNA inhibitors, aimed at restoring SUFU expression to suppress oncogenic signaling (PubMed: 21885924). These therapeutic strategies seek to stabilize the SUFU transcript or block the binding of inhibitory miRNAs to prevent the loss of this essential tumor suppressor. However, challenges remain regarding the delivery of these RNA-targeted agents and the potential for off-target effects within the complex regulatory landscape of the transcriptome. Monitoring biomarkers like GLI1 and PTCH1 expression is essential to evaluate the efficacy of targeting the SUFU 3′-UTR in clinical settings.

Other names

SUFU 3′-UTRSuppressor of fused homolog 3′-untranslated regionSUFU 3-prime UTR

Restoration of SUFU protein levels by preventing miRNA-mediated degradation or translational repression of SUFU mRNA.