METTL16 drives enhanced BCAT1 activity, triggering branched-chain amino acid catabolism in tumor cells and linking metabolism to immune suppression.

METTL16 directly regulates BCAT1 by binding its mRNA and adding m6A marks, stabilizing BCAT1 transcripts and boosting protein levels.

Rescue experiments show that forcing BCAT1 overexpression in METTL16-depleted cells largely reverses tumor-growth suppression and restores CD8+ T cell activity, identifying BCAT1 as the mediator between METTL16, metabolism, and immune evasion.

These findings imply RNA modifications like m6A are central regulators of cancer metabolism and tumor immunology, with METTL16 and BCAT1 as potential biomarkers for immunotherapy responsiveness and targets for combination strategies with checkpoint inhibitors.

In a xenograft model, METTL16 depletion slows tumor growth, lowers Ki-67, and increases CD8+ T cell infiltration and effector molecule levels, confirming METTL16’s dual role in promoting growth and dampening immunity in vivo.

Silencing METTL16 in colorectal cancer cells reduces proliferation, migration, and invasion, and enhances CD8+ T cell–mediated anti-tumor activity in co-culture by boosting T cell proliferation and release of IFN-γ, IL-2, and granzyme B.

METTL16, a nuclear RNA methyltransferase, is elevated in colorectal cancer tumors and promotes tumor growth and immune evasion by reprogramming tumor metabolism.

Branched-chain amino acid metabolism acts as a competitive nutrient mechanism that may limit CD8+ T cell efficacy in tumors, supporting rationale for combining METTL16/BCAT1 targeting with immune checkpoint blockade.