F-box and WD repeat domain containing 7 mRNA 3' untranslated region (FBXW7 mRNA 3'UTR) (FBXW7 mRNA 3'UTR)

The F-box and WD repeat domain containing 7 (FBXW7) mRNA 3' untranslated region (3'UTR) is a pivotal regulatory sequence located at the 3' end of the FBXW7 transcript. FBXW7 itself is a critical tumor suppressor that serves as the substrate-recognition component of the SCF (Skp1-Cullin-F-box) E3 ubiquitin ligase complex, responsible for the proteasomal degradation of several key oncoproteins, including c-Myc, Notch, Cyclin E, and c-Jun (UniProt P63239). The 3'UTR of FBXW7 is a frequent target for oncogenic microRNAs (miRNAs) such as miR-223, miR-25, miR-27a, and miR-129, which bind to complementary sequences within this region to suppress FBXW7 expression via mRNA cleavage or translational inhibition (PubMed: 22508239, 22964311). This downregulation of FBXW7 leads to the accumulation of its oncogenic substrates, thereby promoting cell proliferation, epithelial-mesenchymal transition (EMT), and chemoresistance in various malignancies, including gastric, colorectal, and breast cancers (PubMed: 18632627). Consequently, the FBXW7 mRNA 3'UTR is considered a high-value target for therapeutic intervention using RNA-based technologies, such as antisense oligonucleotides (ASOs) or antagomirs, which aim to block miRNA binding and restore FBXW7-mediated tumor suppression. Current research focuses on identifying specific miRNA-3'UTR interactions that can be disrupted to treat advanced or drug-resistant cancers.

Other names

FBW7 mRNA 3'UTRhCdc4 mRNA 3'UTRSEL10 mRNA 3'UTRAGO mRNA 3'UTRFBXW7 3'UTR

Restoration of FBXW7 protein expression by blocking microRNA-mediated silencing at the 3'UTR.