Erb-B2 receptor tyrosine kinase 3 messenger RNA 3'-untranslated region (ERBB3 mRNA 3'-UTR)

The ERBB3 mRNA 3'-untranslated region (3'-UTR) is a critical regulatory segment of the messenger RNA encoding the HER3 receptor, a member of the epidermal growth factor receptor family (PubMed: 21832179). This region contains specific sequences that serve as binding sites for microRNAs, such as miR-125a and miR-125b, and various RNA-binding proteins that collectively govern the stability and translation efficiency of the ERBB3 transcript (PubMed: 24213919). In many cancers, including breast and lung adenocarcinoma, the loss of negative regulation at the 3'-UTR leads to HER3 protein overexpression, which drives tumor progression and confers resistance to standard-of-care EGFR and HER2 inhibitors (PubMed: 18614392). Therapeutic intervention targeting this region, such as with antisense oligonucleotides (ASOs) like EZN-3920 or microRNA mimics, aims to reduce HER3 protein levels by inducing mRNA degradation or blocking translation (PubMed: 20551321). Because HER3 is a pseudokinase with limited catalytic activity, targeting its expression at the mRNA level offers a strategic advantage over traditional small-molecule inhibitors that target kinase domains. This approach effectively dampens the PI3K/AKT signaling pathway, which is the primary oncogenic output of HER3 heterodimerization.

Other names

HER3 mRNA 3'-UTRErbB3 3'-UTRHuman epidermal growth factor receptor 3 mRNA 3'-UTRERBB3 3'-untranslated region

Antisense-mediated RNase H cleavage of the mRNA transcript or RNA interference (RNAi) leading to degradation and translational repression of the ERBB3 gene product.