ArticleLeukemia2015
MiR-29b replacement inhibits proteasomes and disrupts aggresome+autophagosome formation to enhance the antimyeloma benefit of bortezomib.
Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 78 citations in OpenAlex.
- A novel indirubin- 3-monoxime derivative I3MV- 8b exhibits remarkable cytotoxicity against multiple myeloma by targeting TRIM28.Biomarker research · 2025Article
- NEAT1-mediated regulation of proteostasis and mRNA localization impacts autophagy dysregulation in Rett syndrome.Nucleic acids research · 2025Article
- MicroRNA-665 and its potential role in drug response and survival outcomes in multiple myeloma: a preliminary study.Frontiers in pharmacology · 2025Article
- Acquired Bortezomib Resistance in Multiple Myeloma: From Mechanisms to Strategy.Current treatment options in oncology · 2024Review
- PA200-Mediated Proteasomal Protein Degradation and Regulation of Cellular Senescence.International journal of molecular sciences · 2024Review
- CRIP1 involves the pathogenesis of multiple myeloma via dual-regulation of proteasome and autophagy.EBioMedicine · 2024Article
- Review
- Targeting Proteasomes and the MHC Class I Antigen Presentation Machinery to Treat Cancer, Infections and Age-Related Diseases.Cancers · 2023Review
- Regulation of miRNA expression by α4β1 integrin-dependent multiple myeloma cell adhesion.EJHaem · 2023Article
- Exosome miRNAs profiling in serum and prognostic evaluation in patients with multiple myeloma.Blood science (Baltimore, Md.) · 2023Article
- Shutting off the fuel supply to target metabolic vulnerabilities in multiple myeloma.Frontiers in oncology · 2023Review
- Drug Resistance: The Role of Exosomal miRNA in the Microenvironment of Hematopoietic Tumors.Molecules (Basel, Switzerland) · 2022Review
- The Role of miR-29 Family in TGF-β Driven Fibrosis in Glaucomatous Optic Neuropathy.International journal of molecular sciences · 2022Review
- MiRNA as a Potential Target for Multiple Myeloma Therapy-Current Knowledge and Perspectives.Journal of personalized medicine · 2022Review
- The Proteasome Activator PA200/PSME4: An Emerging New Player in Health and Disease.Biomolecules · 2022Review
- MicroRNAs as a Potential New Preventive Approach in the Transition from Asymptomatic to Symptomatic Multiple Myeloma Disease.Cancers · 2021Review
- Arginine Metabolism and Its Potential in Treatment of Colorectal Cancer.Frontiers in cell and developmental biology · 2021Review
- The Emerging Roles of Autophagy-Related MicroRNAs in Cancer.International journal of biological sciences · 2021Review
- Bortezomib Inhibits Multiple Myeloma Cells by Transactivating ATF3 to Trigger miR-135a-5p- Dependent Apoptosis.Frontiers in oncology · 2021Article
- Role of microRNAs in Diagnosis, Prognosis and Management of Multiple Myeloma.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Evading apoptosis is a cancer hallmark that remains a serious obstacle in current treatment approaches. Although proteasome inhibitors (PIs) have transformed management of multiple myeloma (MM), drug resistance emerges through induction of the aggresome+autophagy pathway as a compensatory protein clearance mechanism. Genome-wide profiling identified microRNAs (miRs) differentially expressed in bortezomib-resistant myeloma cells compared with drug-naive cells. The effect of individual miRs on proteasomal degradation of short-lived fluorescent reporter proteins was then determined in live cells. MiR-29b was significantly reduced in bortezomib-resistant cells as well as in cells resistant to second-generation PIs carfilzomib and ixazomib. Luciferase reporter assays demonstrated that miR-29b targeted PSME4 that encodes the proteasome activator PA200. Synthetically engineered miR-29b replacements impaired the growth of myeloma cells, patient tumor cells and xenotransplants. MiR-29b replacements also decreased PA200 association with proteasomes, reduced the proteasome's peptidase activity and inhibited ornithine decarboxylase turnover, a proteasome substrate degraded through ubiquitin-independent mechanisms. Immunofluorescence studies revealed that miR-29b replacements enhanced the bortezomib-induced accumulation of ubiquitinated proteins but did not reveal aggresome or autophagosome formation. Taken together, our study identifies miR-29b replacements as the first-in-class miR-based PIs that also disrupt the autophagy pathway and highlight their potential to synergistically enhance the antimyeloma effect of bortezomib.
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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.