Histone-lysine N-methyltransferase EZH2 mRNA 3' untranslated region (EZH2 mRNA 3' UTR)

The Histone-lysine N-methyltransferase EZH2 mRNA 3' untranslated region (UTR) is a critical regulatory segment of the EZH2 transcript that governs protein abundance through post-transcriptional mechanisms (Varambally et al., 2008, Science). EZH2 serves as the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2), which silences genes via trimethylation of histone H3 at lysine 27 (H3K27me3) (UniProt Q15910). The 3' UTR contains conserved binding sites for several microRNAs, most notably miR-101 and miR-26a, which act as endogenous regulators by promoting mRNA degradation or inhibiting translation (Sander et al., 2008, Cancer Research). In various malignancies, including prostate and breast cancers, the downregulation of these miRNAs leads to EZH2 overexpression, which in turn promotes tumor cell proliferation, epithelial-to-mesenchymal transition, and stemness (PubMed PMID: 19074340). Therapeutic strategies targeting this region involve the use of miRNA mimics or antisense oligonucleotides (ASOs) to specifically reduce EZH2 protein synthesis, offering a distinct approach from small-molecule inhibitors that target the enzyme's catalytic site. This RNA-level targeting is particularly relevant in cases where EZH2 protein levels drive disease progression independently of its methyltransferase activity.

Other names

Enhancer of zeste homolog 2 mRNA 3' UTREZH2 3'-UTRKMT6 mRNA 3' UTREZH2 3' untranslated region

RNA interference (RNAi) or antisense-mediated degradation and translational repression to reduce EZH2 protein expression.