METTL3 Methylation Induces Decay of Endogenous Retroelement Transcripts to Promote Tumor Immune Evasion - PubMed
3 days ago
- #immune evasion
- #colorectal cancer
- #RNA methylation
- METTL3 methylation at lysine 513 (K513) is linked to colorectal cancer (CRC) progression and recurrence.
- SETD1A catalyzes METTL3 K513 methylation, enhancing its binding to S-adenosylmethionine (SAM) and increasing RNA m6A deposition.
- Methylated METTL3 suppresses endogenous retroelements, impairing type I interferon responses and promoting tumor immune evasion.
- Fluorouracil induces an E2F4/SETD1A/METTL3 regulatory axis, where E2F4 self-regulation activates SETD1A to drive METTL3 methylation.
- Targeting the E2F4/SETD1A/METTL3 axis enhances immune checkpoint blockade (ICB) efficacy, significantly suppressing tumor growth.
- This study reveals a methylation-dependent mechanism reshaping the tumor immune microenvironment, suggesting a new therapeutic strategy for CRC.