Nonsense-mediated mRNA decay inhibits TRAF6-dependent anti-tumor immunity in colorectal cancer.

ABSTRACT: Despite advances in colorectal cancer (CRC) treatment, immunotherapy shows limited efficacy due to low immunogenicity. Nonsense-mediated mRNA decay (NMD) prevents the synthesis of potentially detrimental proteins. While targeting NMD has therapeutic potential, its specific effect on CRC remains uncertain. Our research discovered significant NMD activation and upregulated SMG5 expression in CRC. Inhibition of NMD by small interfering RNA (siRNA) targeting SMG5 or NMD inhibitor NMDI14 remodeled tumor microenvironment (TME) by altering innate immune cells and enhancing CD8⁺ T cells activation. NMD inhibition also activated TBK1 through upregulation of TRAF6, which was targeted by NMD through its elongated 3'-UTR in a non-canonical manner. High SMG5 and low TRAF6 expression are asso

SUBMITTER: Wang Y 

PROVIDER: S-EPMC12765849 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature