Myb proto-oncogene protein mRNA 3′ untranslated region (MYB 3′UTR)

The Myb proto-oncogene protein mRNA 3′ untranslated region (MYB mRNA 3′UTR) is a critical regulatory segment of the MYB transcript that controls the expression of the c-Myb transcription factor (Source: UniProt P10242). This region contains multiple highly conserved binding sites for microRNAs, including miR-15a, miR-16, and miR-150, which act to destabilize the mRNA and inhibit its translation (Source: PubMed 17486091). In various malignancies such as acute myeloid leukemia and adenoid cystic carcinoma, the 3′UTR is frequently lost or truncated due to chromosomal translocations, most notably the MYB-NFIB fusion (Source: PubMed 19234464). The loss of these regulatory sequences allows the MYB gene to escape microRNA-mediated suppression, leading to the oncogenic overexpression of the MYB protein (Source: PubMed 21415924). Because the MYB protein itself is difficult to target with small molecules, the mRNA and its 3′UTR have become focal points for RNA-targeted therapies (Source: PubMed 30217985). Therapeutic interventions include antisense oligonucleotides (ASOs) like ION-251, which are designed to bind the transcript and induce its degradation via RNase H (Source: PubMed 33311587). Additionally, experimental strategies involve the use of microRNA mimics to restore the natural post-transcriptional repression of MYB in cancer cells (Source: PubMed 26437233). However, a major challenge in targeting this region is the essential role of MYB in normal hematopoiesis, meaning that potent inhibition can lead to severe side effects such as anemia and thrombocytopenia (Source: PubMed 21415924).

Other names

c-Myb 3′UTRMYB 3-prime untranslated regionv-myb avian myeloblastosis viral oncogene homolog 3′UTRMYB 3′ untranslated region

Antisense-mediated mRNA degradation and miRNA-mediated translational repression