biostudies-literatureLiu QZThe Science and Technology Commission of Shanghai Hongkou District"Special fund for scientific research startup" by Shanghai Fourth People's Hospitalmedical engineering of Shanghai Jiao Tong University1749-1762https://www.ebi.ac.uk/biostudies/studies/S-EPMC11145145biostudies-literatureUnknown115(6)N⁶-Methyladenosine (m⁶A) is a important process regulating gene expression post-transcriptionally. Programmed death ligand 1 (PD-L1) is a major immune inhibitive checkpoint that facilitates immune evasion and is expressed in tumor cells. In this research we discovered that Wilms' tumor 1-associated protein (WTAP) degradation caused by ubiquitin-mediated cleavage in cancer cells (colorectal cancer, CRC) under hypoxia was inhibited by Pumilio homolog 1 (PUM1) directly bound to WTAP. WTAP enhanced PD-L1 expression in a way that was m⁶A-dependent. m⁶A "reader," Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) identified methylated PD-L1 transcripts and subsequently fixed its mRNA. Additionally, we found that T-cell proliferation and its Cancer scienceWTAP-induced N⁶-methyladenosine of PD-L1 blocked T-cell-mediated antitumor activity under hypoxia in colorectal cancer.PMC11145145sykyqd04401 and sykyqd05101YG2022QN115hongwei2202-19Huang ZXQiao GLZhou MJChen ZZhang NChen JYZhou DHTu XHXie YXLiu QZfalseWTAP-induced N⁶-methyladenosine of PD-L1 blocked T-cell-mediated antitumor activity under hypoxia in colorectal cancer.N⁶-Methyladenosine (m⁶A) is a important process regulating gene expression post-transcriptionally. Programmed death ligand 1 (PD-L1) is a major immune inhibitive checkpoint that facilitates immune evasion and is expressed in tumor cells. In this research we discovered that Wilms' tumor 1-associated protein (WTAP) degradation caused by ubiquitin-mediated cleavage in cancer cells (colorectal cancer, CRC) under hypoxia was inhibited by Pumilio homolog 1 (PUM1) directly bound to WTAP. WTAP enhanced PD-L1 expression in a way that was m⁶A-dependent. m⁶A "reader," Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) identified methylated PD-L1 transcripts and subsequently fixed its mRNA. Additionally, we found that T-cell proliferation and its 2024-01-01T00:00:00Z2024 Jun2026-06-02T06:09:15.837Z2026-04-15T03:10:06.799ZS-EPMC111451453850821710.1111/cas.16136