Collateral lethality: A unique type of synthetic lethality in cancers DOI
Zichen Zhao, Lingling Zhu, Yu Luo

et al.

Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 265, P. 108755 - 108755

Published: Nov. 23, 2024

Language: Английский

Alternative Splicing: A Key Regulator in T cell Response and Cancer Immunotherapy DOI Creative Commons

C.-C. Yong,

Yexin Liang,

Minmin Wang

et al.

Pharmacological Research, Journal Year: 2025, Volume and Issue: unknown, P. 107713 - 107713

Published: March 1, 2025

Language: Английский

Citations

1
PRMT5 inhibitors: Therapeutic potential in pancreatic cancer DOI
Carolin Schneider,

Valentina Spielmann,

Christian Braun

et al.

Translational Oncology, Journal Year: 2025, Volume and Issue: 55, P. 102366 - 102366

Published: March 30, 2025

Language: Английский

Citations

0
PRMT3 drives PD-L1-mediated immune escape through activating PDHK1-regulated glycolysis in hepatocellular carcinoma DOI Creative Commons

Chen‐Hong Ding,

Fang‐Zhi Yan,

Binghe Xu

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 6, 2025

Aberrant expression of programmed death ligand-1 (PD-L1) facilitates tumor immune evasion. Protein arginine methyltransferase 3 (PRMT3), a member type I PRMT family, mediates asymmetric dimethylarginine (ADMA) modification various substrate proteins. This study investigates the role PRMT3 in PD-L1-associated immunosuppression hepatocellular carcinoma (HCC). Hepatocyte-specific knockout Prmt3 significantly suppressed HCC progression DEN-CCL4-treated mice. Knockout cells markedly increased CD8+ T cell infiltration, and reduced lactate production tumors. interacted with pyruvate dehydrogenase kinase 1 (PDHK1), dimethylation PDHK1 at 363 368 residues its activity. The R363/368 K mutant or inhibition by JX06 blocked effect on production. treatment also attenuated tumor-promoting vitro vivo. Furthermore, RNA-seq analysis revealed that downregulates tumor-associated checkpoint, PD-L1, tissues. Chromatin immunoprecipitation (ChIP) assay demonstrated promotes lactate-induced PD-L1 enhancing direct binding histone H3 lysine 18 lactylation (H3K18la) to promoter. Tissue microarray showed positive correlation between patients. Anti-PD-L1 reversed PRMT3-induced growth restored infiltration. Our research links PRMT3-mediated metabolic reprogramming evasion, revealing PRMT3-PDHK1-lactate-PD-L1 axis may be potential target for improving efficacy immunotherapy HCC.

Language: Английский

Citations

0
Collateral lethality: A unique type of synthetic lethality in cancers DOI
Zichen Zhao, Lingling Zhu, Yu Luo

et al.

Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 265, P. 108755 - 108755

Published: Nov. 23, 2024

Language: Английский

Citations

0