Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Diffuse large B-cell lymphoma (DLBCL), the most common B-cell non-Hodgkin lymphoma (B-NHL), is characterized by strong aggression, high heterogeneity, and poor prognosis. Consequently, there is an urgent need to identify crucial therapeutic targets. Here, we found that the transcription factor zinc-finger and homeobox 2 (ZHX2) was highly expressed in DLBCL. Subsequently, ZHX2 was proven to be critical for promoting DLBCL cell proliferation by inhibiting ferroptosis. Mechanistically, ZHX2 bound to the promoter region of the solute carrier family 3-member 2 (SLC3A2) gene through liquid-liquid phase separation (LLPS) and activated its function to negatively regulate ferroptosis. Furthermore, we constructed lipid nanoparticles ZHX2-siRNA@LNP targeting DLBCL, which effectively inhibited the growth of the tumors in vivo. In summary, our study indicated that the LLPS of ZHX2 protected DLBCL against ferroptosis through induction of SLC3A2, and disturbing it with ZHX2-siRNA@LNP could significantly repress DLBCL, providing a promising therapeutic strategy for DLBCL.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/s41375-025-02718-z | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Distribution and Relative Size of Protein Binding Domains Cooperatively Influence Phase Separation of Protein-RNA Mixtures.
J Phys Chem B
September 2025
Hefei National Research Center for Physical Sciences at the Microscale and Key Laboratory of Precision and Intelligent Chemistry, Department of Chemical Physics, University of Science and Technology of China, Hefei, Anhui 230026, China.
Multivalent protein-protein interactions play essential roles in mediating liquid-liquid phase separation (LLPS) that drives biomolecular condensate formation. Here, we systematically investigate how the spatial distribution and relative size of protein binding domains (PBDs) would influence LLPS in a mixture of spherical proteins and RNA single strands by using a patchy-particle polymer model, wherein each protein contains a fixed number of PBDs on the surface distributed closely or sparsely. Intriguingly, we find that LLPS behavior exhibits a nontrivial dependence on the cooperative interplay between PBD distribution and protein size: while sparsely distributed PBDs are more favorable to LLPS for small proteins, closely packed PBDs facilitate LLPS for larger counterparts.
View Article and Find Full Text PDFDissecting the Molecular Determinants of α-synuclein Phase Separation and Condensate Aging: The Pivotal Role of β-Sheet-Rich Motifs.
Adv Sci (Weinh)
September 2025
Department of Physics, State Key Laboratory of Surface Physics, and Key Laboratory for Computational Physical Science (Ministry of Education), Fudan University, 2005 Songhu Road, Yangpu District, Shanghai, 200433, China.
Emerging evidence indicates that liquid-liquid phase separation of α-synuclein occurs during the nucleation step of its aggregation, a pivotal step in the onset of Parkinson's disease. Elucidating the molecular determinants governing this process is essential for understanding the pathological mechanisms of diseases and developing therapeutic strategies that target early-stage aggregation. While previous studies have identified residues critical for α-synuclein amyloid formation, the key residues and molecular drivers of its phase separation remain largely unexplored.
View Article and Find Full Text PDFMapping the structural changes of LCD-TDP43 during the liquid-liquid phase separation by different spectroscopic platforms.
Biophys Chem
September 2025
Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
A comprehensive understanding of the molecular mechanism underlying the Liquid-Liquid Phase Separation (LLPS) pathway of LCD-TDP43 remains a challenge in the context of its neuropathogenesis. The primary driving force behind the TDP-43 LLPS is the interplay of hydrophobic interactions reinforced by aromatic residues. This study presents a novel, convenient, sensitive, and probe-free approach using excitation-emission matrix (EEM) fluorescence to monitor the microenvironment of aromatic residues and π-π stacking interactions during different stages of the LLPS pathway.
View Article and Find Full Text PDFUnveiling the role of biomolecular condensates in cellular function and cancer.
Adv Biol Regul
September 2025
Laboratory of Cancer Cell Architecture, Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic. Electronic address:
Biomolecular condensates (BMCs) are membrane-less organelles formed through liquid-liquid phase separation, primarily driven by multivalent interactions between scaffold and client molecules. These dynamic compartments enable cells to spatially and temporally organize biochemical reactions by locally concentrating specific biomolecules, thereby enhancing the frequency of productive molecular interactions and increasing reaction rates. BMCs are integral to normal cellular physiology, with well-characterized examples including the nucleolus and Cajal bodies.
View Article and Find Full Text PDFSalicylic acid reduces ELF3 phase separation and suppresses thermomorphogenic growth in Arabidopsis.
Plant J
September 2025
Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, Singapore, 117604, Singapore.
Salicylic acid (SA), a long-characterized defense hormone, is increasingly recognized for its roles in plant growth and development. However, its involvement in mediating plant growth responses to environmental cues remains less understood. Here, we show that SA negatively affects thermomorphogenic growth in Arabidopsis thaliana.
View Article and Find Full Text PDF