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Liquid-liquid phase separation of ZHX2 protects DLBCL cells against ferroptosis through induction of SLC3A2 [RNA-seq]

GSE292498 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2025/07/30 Platform GPL24676
Summary
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 homeoboxes 2 (ZHX2) is highly expressed in DLBCL. Subsequently, ZHX2 was proven to be critical for promoting DLBCL cells proliferation by inhibiting ferroptosis. Mechanistically, ZHX2 binds to the promoter region of the solute carrier family 3-member 2 (SLC3A2) gene through liquid-liquid phase separation (LLPS) and activates its function to negatively regulate ferroptosis. Furthermore, we constructed lipid nanoparticles Zhx2-siRNA@LNP targeting DLBCL, which effectively inhibited the growth of the tumor in vivo. In summary, our study indicated that LLPS of ZHX2 protects 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.
Published in
Liquid-liquid phase separation of ZHX2 protects DLBCL cells against ferroptosis through induction of SLC3A2
Zhang J, Wang D, Luan M et al. · Leukemia 2025 · PMID 40730912 · doi:10.1038/s41375-025-02718-z
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Also filed as BioProject PRJNA1238867 and SRA study SRP571920. Searching any of these in the dataset finder brings you back here.

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