ArticleCancer gene therapy2023
SUMOylation inhibition enhances multiple myeloma sensitivity to lenalidomide.
Article in Cancer gene therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- A succinylation-based classifier predicts chemotherapy response in prostate cancer and reveals KAT2A as a therapeutic target.Clinical and translational medicine · 2026Article
- SUMOylation is destined for regulatory T cell-related immune dysregulation.Cell death discovery · 2026Review
- Quercetin and hematological cancers: where are we and where are we going?Molecular biology reports · 2025Review
- Small molecule inhibition of SUMOylation increases expression from AAV vectors both during and after initial transduction in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Immune regulation by the SUMO family.Nature reviews. Immunology · 2025Review
- Post-Translational Modifications in Multiple Myeloma: Mechanisms of Drug Resistance and Therapeutic Opportunities.Biomolecules · 2025Review
- Reposition of lenalidomide as a radiation protector based on LINCS gene expression signatures and its preclinical validation.Scientific reports · 2025Article
- MLN0905, a new inhibitor of Polo-like kinase 1 (PLK1), enhances the efficiency of lenalidomide in promoting the apoptosis of multiple myeloma cell lines.Investigational new drugs · 2025Article
- The impact of dysregulation SUMOylation on prostate cancer.Journal of translational medicine · 2025Review
- Ginkgolic acid regulates myogenic development by influencing the proliferation and differentiation of C2C12 myoblast cells.Molecular medicine reports · 2024Article
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
- Targeted inhibition of SUMOylation: treatment of tumors.Human cell · 2024Review
- SUMOylation inhibitor TAK-981 (subasumstat) synergizes with 5-azacytidine in preclinical models of acute myeloid leukemia.Haematologica · 2024Article
- Paradoxes of Cellular SUMOylation Regulation: A Role of Biomolecular Condensates?Pharmacological reviews · 2023Review
- Lenalidomide in Multiple Myeloma: Review of Resistance Mechanisms, Current Treatment Strategies and Future Perspectives.Cancers · 2023Review
- PPAR agonists attenuate lenalidomide's anti-myeloma activity in vitro and in vivo.Cancer letters · 2022Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Despite the potent effect of lenalidomide (Len) in multiple myeloma (MM) treatment, patients develop Len resistance leading to progressive disease, demanding an urgent need to investigate the mechanisms mediating Len resistance. Our study identified SUMOylation as a potential mechanism regulating Len resistance in MM. Len-resistant MM cell line MMR10R presented much higher SUMO E1 (SAE2) expression and more global SUMOylation than Len-sensitive MM1S cell line. SUMOylation inhibition by using TAK-981, a novel and specific SUMO E1 inhibitor, significantly enhances myeloma sensitivity to Len in MM cell lines. Moreover, the enhanced anti-MM activity by TAK-981 and Len combination has been validated using primary relapsing MM patient samples. Overexpression of IRF4 and c-Myc is a major mechanism of Len resistance. Len showed limited effect on IRF4 and c-Myc level in Len-resistance cell line, but TAK-981 treatment reduced IRF4 and c-Myc expression in Len-resistant line and caused further decrease when combined with Len. We found SUMOylation inhibition decreases IRF4 at transcriptional and post-translational level. SUMOylation inhibition reduced DOT1L with decreased methylation of histone H3 lysine 79, to suppress IRF4 gene transcription. SUMOylation inhibition also reduced IRF4 protein level by enhancing degradation. Overall, our data revealed SUMOylation inhibition enhances Len sensitivity through downregulating IRF4.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.