ArticleLeukemia2018
Dysregulation of EZH2/miR-138 axis contributes to drug resistance in multiple myeloma by downregulating RBPMS.
Article in Leukemia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 76 citations in OpenAlex.
- Structural characteristics and SARs of EZH2 inhibitors.Molecular diversity · 2026Review
- A novel epigenetic regulation of JAM-A by EZH2-DNMT3A cascade contributes to T cell adhesion via the activation of Rap1a in lupus patients.Journal of translational autoimmunity · 2026Article
- Deciphering epigenetic crosstalk in multiple myeloma pathogenesis and treatment.Clinical epigenetics · 2026Review
- Multiple myeloma associated long non-coding RNA PLUM confers chemoresistance by enhancing PRC2 mediated UPR pathway activation.Nature communications · 2025Article
- The de novo DNA methyltransferase 3B is a novel epigenetic regulator of MYC in multiple myeloma, representing a promising therapeutic target to counter relapse.Journal of experimental & clinical cancer research : CR · 2025Article
- Polycomb repressive complex 2 (PRC2) pathway's role in cancer cell plasticity and drug resistance.Functional & integrative genomics · 2025Review
- RBPMS inhibits bladder cancer metastasis by downregulating MYC pathway through alternative splicing of ANKRD10.Communications biology · 2025Article
- Acquired Bortezomib Resistance in Multiple Myeloma: From Mechanisms to Strategy.Current treatment options in oncology · 2024Review
- Article
- Current Technologies Unraveling the Significance of Post-Translational Modifications (PTMs) as Crucial Players in Neurodegeneration.Biomolecules · 2024Review
- Therapeutic targeting potential of the protein lysine and arginine methyltransferases to reverse cancer chemoresistance.Frontiers in molecular biosciences · 2024Review
- SKping cell cycle regulation: role of ubiquitin ligase SKP2 in hematological malignancies.Frontiers in oncology · 2024Review
- Tumor-suppressive functions of protein lysine methyltransferases.Experimental & molecular medicine · 2023Review
- TRIM21 enhances bortezomib sensitivity in multiple myeloma by halting prosurvival autophagy.Blood advances · 2023Article
- Study on the Effect of EZH2 Inhibitor Combined with TIGIT Monoclonal Antibody against Multiple Myeloma Cells.International journal of molecular sciences · 2023Article
- Targeting miRNAs and Other Non-Coding RNAs as a Therapeutic Approach: An Update.Non-coding RNA · 2023Review
- circEZH2Cancer science · 2023Article
- Melatonin and 5-fluorouracil combination chemotherapy: opportunities and efficacy in cancer therapy.Cell communication and signaling : CCS · 2023Review
- Increased Expression of the RBPMS Splice Variants Inhibits Cell Proliferation in Ovarian Cancer Cells.International journal of molecular sciences · 2022Article
- Progranulin regulates the development and function of NKT2 cells through EZH2 and PLZF.Cell death and differentiation · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
EZH2 is highly expressed in multiple myeloma (MM). However, the molecular mechanisms underlying EZH2 overexpression and its role in drug resistance of MM remain undefined. Here we show that EZH2 is upregulated in drug-resistant MM cells and its aberrant overexpression is associated with poor prognosis of MM patients. Overexpression of EZH2 in parental MM cells renders them resistant to anti-myeloma drugs and suppression of EZH2 displays the opposite effects. Using miRNA target scan algorithms, we identify miR-138 as a regulator of EZH2, which is conversely repressed by EZH2-induced H3K27 trimethylation in MM-resistant cell lines and primary tumor cells. Analysis of ChIP-seq dataset and H3K27me3 ChIP reveals that RBPMS is a direct and functionally relevant target of EZH2. RBPMS silencing confers resistance to MM cells and restoration of RBPMS by miR-138 overexpression re-sensitizes the resistant cells to drug. Importantly, in vivo delivery of miR-138 mimics or pharmacological inhibitor of EZH2 in combination with a proteasome inhibitor, bortezomib, induces significant regression of tumors in xenograft model. This study establishes EZH2/miR-138 axis as a potential therapeutic target for MM.
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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.