ArticleScientific reports2020
Silencing of SENP2 in Multiple Myeloma Induces Bortezomib Resistance by Activating NF-κB Through the Modulation of IκBα Sumoylation.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Phosphoproteomic Profiling of Multiple Myeloma Based on Ex Vivo Drug Sensitivity Resistance Testing Identifies Phosphorylation Signatures Associated with Drug Response.Biomolecules · 2026Article
- Mechanisms and intervention strategies of microenvironment-mediated drug resistance in multiple myeloma.Cancer cell international · 2026Review
- DeSUMOylation of IGF2BP2 Promotes Neuronal Differentiation of OM-MSCs by Stabilizing SOX11 to Ameliorate Brain Injury After Intracerebral Hemorrhage.CNS neuroscience & therapeutics · 2025Article
- Post-Translational Modifications in Multiple Myeloma: Mechanisms of Drug Resistance and Therapeutic Opportunities.Biomolecules · 2025Review
- Establishment of a SUMO pathway related gene signature for predicting prognosis, chemotherapy response and investigating the role of EGR2 in bladder cancer.Journal of Cancer · 2024Article
- SUMOylation inhibition overcomes proteasome inhibitor resistance in multiple myeloma.Blood advances · 2023Article
- Cancer-Associated Dysregulation of Sumo Regulators: Proteases and Ligases.International journal of molecular sciences · 2022Review
- HAPLN1 confers multiple myeloma cell resistance to several classes of therapeutic drugs.PloS one · 2022Article
- Novel insights into the impact of the SUMOylation pathway in hematological malignancies (Review).International journal of oncology · 2021Review
- Review
- Research progress in proteasome inhibitor resistance to multiple myeloma.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2021Article
- Review
- Hypomethylating Chemotherapeutic Agents as Therapy for Myelodysplastic Syndromes and Prevention of Acute Myeloid Leukemia.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Current Methods of Post-Translational Modification Analysis and Their Applications in Blood Cancers.Cancers · 2021Review
- The Landscape of Signaling Pathways and Proteasome Inhibitors Combinations in Multiple Myeloma.Cancers · 2021Review
- Expression and correlation of IL-2, IL-10 and TNF-α in patients with multiple myeloma-infected herpes zoster treated by bortezomib-containing regimen.American journal of translational research · 2021Article
- Ubiquitination and Ubiquitin-Like Modifications in Multiple Myeloma: Biology and Therapy.Cancers · 2020Review
- Protein Kinase D 1 Predicts Poor Treatment Response and Unfavorable Survival of Bortezomib-Based Treatment, and Its Knockdown Enhances Drug Sensitivity to Bortezomib in Multiple Myeloma.Technology in cancer research & treatmentArticle
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The proteasome inhibitor bortezomib is the most successfully applied chemotherapeutic drug for treating multiple myeloma. However, its clinical efficacy reduced due to resistance development. The underlying molecular mechanisms of bortezomib resistance are poorly understood. In this study, by combining in silico analysis and sgRNA library based drug resistance screening assay, we identified SENP2 (Sentrin/SUMO-specific proteases-2) as a bortezomib sensitive gene and found its expression highly downregulated in bortezomib resistant multiple myeloma patient's samples. Furthermore, down regulation of SENP2 in multiple myeloma cell line RPMI8226 alleviated bortezomib induced cell proliferation inhibition and apoptosis, whereas, overexpression of SENP2 sensitized these cells to bortezomib treatment. We further demonstrate that knockdown of SENP2 in RPMI8226 cells increased SUMO2 conjugated IκBα that resulted in the activation of NF-κB. Taken together, we report that silencing of SENP2 and consequent activation of NF-κB through the modulation of IκBα sumoylation as a novel mechanism inducing bortezomib resistance in multiple myeloma.
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