Inhibition of tumor-intrinsic NAT10 enhances antitumor immunity by triggering type I interferon response via MYC/CDK2/DNMT1 pathway.

ABSTRACT: Posttranscriptional modifications are involved in cancer progression. However, the function and regulatory mechanism of mRNA acetylation modification remains largely unknown. Here, we discover an unexpected role of N4-acetylcytidine (ac4C) RNA acetyltransferase NAT10 in reshaping the tumor immune microenvironment. By analyzing patients' data, we find that NAT10 is upregulated in tumor tissues, and negatively correlated with immune cell infiltration and overall survival. Loss of tumoral NAT10 enhances tumor-specific cellular immune response and suppresses tumor growth. Mechanistically, MYC is identified as a key downstream target of NAT10 via enhancing mRNA ac4C modification. Inhibition of NAT10 blocks the MYC/CDK2/DNMT1 pathway, enhances double-stranded RNA (dsRNA) formation, which trigger

SUBMITTER: Liu WC 

PROVIDER: S-EPMC12134272 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature