One-cut homeobox family messenger RNA 3' untranslated regions (ONECUT 3'UTRs)

The ONECUT family mRNAs 3' untranslated regions (3'UTRs) serve as essential regulatory hubs for the post-transcriptional control of One-cut homeobox transcription factors, specifically ONECUT1 (HNF6), ONECUT2, and ONECUT3. These regions are characterized by conserved binding sites for microRNAs, such as miR-124, which modulate mRNA stability and translation to ensure proper tissue development and metabolic homeostasis (Lannoy et al., 2000, PubMed: 10806341). In the context of oncology, dysregulation of these 3'UTRs—often through microRNA depletion or alternative polyadenylation—results in the pathological overexpression of ONECUT proteins. For instance, ONECUT2 overexpression is a hallmark of neuroendocrine prostate cancer (NEPC) and is associated with increased metastatic potential and lineage plasticity (Guo et al., 2019, PubMed: 31142862). Therapeutic strategies targeting these 3'UTRs involve the use of microRNA mimics or antisense oligonucleotides (ASOs) to restore inhibitory control and suppress the oncogenic driver activity of the ONECUT family (Sun et al., 2018, PubMed: 29754081). While promising, challenges include achieving tissue-specific delivery and avoiding off-target effects inherent to modulating broad-acting transcription factor networks.

Other names

ONECUT1 3'UTRONECUT2 3'UTRONECUT3 3'UTRHNF6 3'UTRHNF-6 3'UTROC-1 3'UTROC-2 3'UTROC-3 3'UTR

Binding of microRNA mimics or antisense oligonucleotides to the 3'UTR sequence induces mRNA degradation or inhibits translation, thereby reducing the expression of ONECUT transcription factors.