L-methionine promotes CD8⁺ T cells killing hepatocellular carcinoma by inhibiting NR1I2/PCSK9 signaling.

ABSTRACT:

Background

Liver cancer has consistently high incidence and mortality rates among malignant tumors. PCSK9, a target for hypercholesterolemia therapy, has recently been identified as an inhibitor of anti-tumor immunity, and targeting PCSK9 effectively inhibits tumor progression. However, small molecule inhibitors are lacking due to its flat protein structure.

Methods

PCSK9 transcription inhibitor screening was conducted using a PCSK9 promoter-driven td-Tomato plasmid. Quantitative real-time PCR and immunoblotting were employed to assess the effect of L-methionine on PCSK9 expression in HCC cell lines. Co-culture experiments were performed to evaluate the impact of L-methionine on CD8⁺ T cell-mediated killing of liver cancer cells. RNA sequencing, CUT&Tag, gene edit

SUBMITTER: Yuan C 

PROVIDER: S-EPMC11997342 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature