Reading view
Unveiling Language Routing Isolation in Multilingual MoE Models for Interpretable Subnetwork Adaptation
Route-Induced Density and Stability (RIDE): Controlled Intervention and Mechanism Analysis of Routing-Style Meta Prompts on LLM Internal States
Correction: The multifunctional RNA helicase DDX39A drives glioblastoma progression by modulating WISP1 alternative splicing that induces an immunosuppressive macrophage polarization
Oncogene, Published online: 01 April 2026; doi:10.1038/s41388-026-03756-2
Correction: The multifunctional RNA helicase DDX39A drives glioblastoma progression by modulating WISP1 alternative splicing that induces an immunosuppressive macrophage polarizationInactivating <i>SnRK1β1A</i> promotes broad-spectrum disease resistance in rice
Nature, Published online: 25 March 2026; doi:10.1038/s41586-026-10273-5
SnRK1β1A in rice promotes susceptibility to multiple fungal diseases, and disrupting this infection-inducible gene confers broad-spectrum resistance without compromising growth or yield under normal field conditions.PAK4 functions as an immune suppressor by reprogramming the phosphatidylcholine metabolism of CD8 + T cells within the glioblastoma tumor microenvironment
Oncogene, Published online: 23 March 2026; doi:10.1038/s41388-026-03734-8
PAK4 functions as an immune suppressor by reprogramming the phosphatidylcholine metabolism of CD8 + T cells within the glioblastoma tumor microenvironmentSIRT3 deacetylates STEAP4 to modulate cuproptosis sensitivity via mitochondrial metabolic reprogramming in HBV-related HCC
Cell Death Differ. 2026 Mar 16. doi: 10.1038/s41418-026-01713-w. Online ahead of print.
ABSTRACT
Hepatitis B virus (HBV) infection remains a leading etiological driver of hepatocellular carcinoma (HCC). Cuproptosis is a recently defined copper-dependent form of regulated cell death that selectively eliminates mitochondria-dependent cells; whether HBV rewires this vulnerability remains unknown. Here we unveil a novel HBV X protein (HBx)-driven mechanism of cuproptosis evasion. Integrative analysis of clinical specimens, HBx-transgenic (HBx-Tg) mice, and multi-omics datasets revealed marked downregulation of STEAP4 (six-transmembrane epithelial antigen of prostate 4), a metalloreductase essential for cuproptosis sensitivity, in HBV-positive HCC. Mechanistically, HBx attenuates sirtuin 3 (SIRT3), impairing deacetylation of STEAP4 at lysine 404 and abolishing its mitochondrial targeting. Consequently, cells switch from the tricarboxylic acid (TCA) cycle respiration to glycolysis, reducing sensitivity to the copper ionophore elesclomol (ES). Restoring STEAP4 expression or pharmacological activation of SIRT3 with honokiol (HKL) re-instated mitochondrial STEAP4 localization and re-sensitized HBV-related HCC cells to cuproptosis; combination with ES produced synergistic tumor suppression in vitro and in orthotopic models. Collectively, our findings establish the SIRT3-STEAP4 axis as a novel regulator of cuproptosis resistance in HBV-related HCC. HBx-mediated repression of SIRT3 disrupts STEAP4 deacetylation and mitochondrial targeting, fostering metabolic reprogramming and evasion of copper-induced cell death. The results provide a pre-clinical rationale for copper-directed combination strategies in HBV-associated HCC.
PMID:41840161 | DOI:10.1038/s41418-026-01713-w
LycheeCluster: Efficient Long-Context Inference with Structure-Aware Chunking and Hierarchical KV Indexing
Unveiling Downstream Performance Scaling of LLMs: A Clustering-Based Perspective
PMM2 interacts with TRIM28 to recruit E2F4 and promote KIFC3-mediated tumor glycolysis and colorectal cancer progression
Oncogene, Published online: 06 March 2026; doi:10.1038/s41388-026-03707-x
PMM2 interacts with TRIM28 to recruit E2F4 and promote KIFC3-mediated tumor glycolysis and colorectal cancer progression