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Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
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USP13 dictates Ran turnover and vulnerability to ferroptosis in diffuse large B cell lymphoma (DLBCL)
Xuan Qiao1, Xingmeng Yang1, Yuanhao Diao1
1College of Pharmaceutical Sciences, Southwest University, Chongqing, China.
Cell Death & Disease
|November 28, 2025
Summary
USP13 deubiquitinates Ran in Diffuse Large B-cell Lymphoma (DLBCL), a lethal cancer. Inhibiting USP13 with Spautin-1 synergizes with chemotherapy to induce ferroptosis, offering new therapeutic hope for DLBCL patients.
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- Diffuse Large B-cell Lymphoma (DLBCL) is a prevalent and aggressive B-cell malignancy with high relapse rates and limited treatment options.
- Deubiquitinases (DUBs) play a critical role in cancer by stabilizing oncoproteins, making them potential therapeutic targets.
Purpose of the Study:
- To identify and characterize novel DUBs involved in DLBCL pathogenesis.
- To investigate the role of USP13 in DLBCL and its potential as a therapeutic target.
Main Methods:
- LC-MS/MS and AlphaFold3 modeling to identify USP13 substrates and interactions.
- Pharmacological inhibition (Spautin-1) and genetic manipulation of USP13.
- RNA-sequencing to identify downstream pathways affected by USP13 inhibition.
- In vitro and in vivo experiments to assess therapeutic efficacy and mechanisms.
Main Results:
- USP13 was identified as an overexpressed DUB in DLBCL, critical for disease pathogenesis.
- USP13 deubiquitinates Ran GTPase, modulating its stability and ubiquitination.
- USP13 inhibition affected NF-κB and Notch pathways, implicated in chemoresistance.
- Spautin-1 synergized with Doxorubicin or Cyclophosphamide to induce ferroptosis in DLBCL with minimal organ toxicity.
Conclusions:
- USP13 plays a significant role in DLBCL by deubiquitinating Ran.
- Combined treatment with Spautin-1 and standard chemotherapies (Doxorubicin or Cyclophosphamide) shows promise for DLBCL treatment by inducing ferroptosis.
- This combinational approach offers a potential new therapeutic strategy for combating DLBCL.
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