Programmed death-ligand 1 mRNA 3' untranslated region (CD274 mRNA 3'UTR) (CD274 mRNA 3'UTR)

The Programmed death-ligand 1 mRNA 3' untranslated region (CD274 mRNA 3'UTR) is a critical regulatory segment of the CD274 transcript that governs the stability and translation of the PD-L1 protein (Kataoka et al., Nature 2016). This region contains multiple binding sites for microRNAs (miRNAs), such as miR-513 and miR-200, and RNA-binding proteins (RBPs) like AUF1 and HuR, which normally suppress PD-L1 expression to maintain immune homeostasis (Wang et al., Gene 2017). In various cancers, including T-cell lymphomas and gastric cancer, the 3'UTR of CD274 is frequently truncated or mutated, leading to the loss of these inhibitory regulatory elements and subsequent massive overexpression of PD-L1, which facilitates immune evasion by the tumor (Kataoka et al., Nature 2016). Consequently, the CD274 mRNA 3'UTR has emerged as a novel therapeutic target for RNA-based interventions, including antisense oligonucleotides (ASOs) and small molecules designed to restore regulatory control or induce mRNA degradation (Coelho et al., Trends in Cancer 2017). Targeting this region offers a potential strategy to modulate the PD-1/PD-L1 axis at the post-transcriptional level, potentially overcoming resistance to traditional monoclonal antibody therapies (Mezzadra et al., Nature 2017).

Other names

PD-L1 mRNA 3'UTRB7-H1 mRNA 3'UTRCD274 3' untranslated regionPDCD1L1 mRNA 3'UTR

Modulation of mRNA stability and translation through recruitment of RNase H or steric hindrance of regulatory protein/miRNA binding to the 3' untranslated region.