ArticleOncogene2022
Deubiquitylase USP12 induces pro-survival autophagy and bortezomib resistance in multiple myeloma by stabilizing HMGB1.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 37 citations in OpenAlex.
- High mobility group box 1 and its post-translational modifications: Molecular mechanisms underlying neurodegenerative disease pathogenesis.Neural regeneration research · 2026Article
- E3 Ligases and Deubiquitinases in Controlling High-Mobility Group Box (HMGB) Protein Functions.International journal of molecular sciences · 2026Review
- An oncolytic vaccinia virus encoding CD47 nanobody potentiates antitumor immunity in multiple myeloma.iScience · 2026Article
- USP1 driven mitotic dysregulation and PLK1 stabilization confer Lenvatinib resistance in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2026Article
- The redox-sensitive protein HMGB1: intracellular and extracellular roles.Experimental & molecular medicine · 2026Review
- HMGB1: A Central Node in Cancer Therapy Resistance.International journal of molecular sciences · 2025Review
- circKCNQ5 promotes the proliferation of DNA-methyltransferase 3A R882 mutated acute myeloid leukemia cells by elevating high-mobility group box 1 expression.Annals of medicine · 2025Article
- Dualistic Roles of High Mobility Group Box 1 in Cancer and Inflammation.Cancer medicine · 2025Review
- MIR4726Cell communication and signaling : CCS · 2025Article
- Role of the USP family in autophagy regulation and cancer progression.Apoptosis : an international journal on programmed cell death · 2025Review
- Post-Translational Modifications in Multiple Myeloma: Mechanisms of Drug Resistance and Therapeutic Opportunities.Biomolecules · 2025Review
- The Transcription Axes ERK-Elk1, JNK-cJun, and JAK-STAT Promote Autophagy Activation and Proteasome Inhibitor Resistance in Prostate Cancer Cells.Current issues in molecular biology · 2025Article
- High-mobility group box 1 in acute kidney injury.Frontiers in pharmacology · 2025Review
- Disrupting USP39 deubiquitinase function impairs the survival and migration of multiple myeloma cells through ZEB1 degradation.Journal of experimental & clinical cancer research : CR · 2024Article
- Identification of USP2 as a novel target to induce degradation of KRAS in myeloma cells.Acta pharmaceutica Sinica. B · 2024Article
- Review
- Acquired Bortezomib Resistance in Multiple Myeloma: From Mechanisms to Strategy.Current treatment options in oncology · 2024Review
- IGF2BP3 modified GLI2 transcriptionally regulates SYVN1 and facilitates sepsis liver injury through autophagy.iScience · 2024Article
- Drug resistance mechanisms and treatment strategies mediated by Ubiquitin-Specific Proteases (USPs) in cancers: new directions and therapeutic options.Molecular cancer · 2024Review
- Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the establishment of novel therapeutic interventions, multiple myeloma (MM) remains invariably incurable due to development of drug resistance and subsequent relapse, which are attributed to activation of oncogenic pathways such as autophagy. Deubiquitinating enzymes (DUBs) are promising targets to overcome resistance to proteasome inhibitor-based treatment. Ubiquitin-specific protease-12 (USP12) is a DUB with a known prognostic value in several cancers. We found that USP12 protein levels were significantly higher in myeloma patient samples than in non-cancerous human samples. Depletion of USP12 suppressed cell growth and clonogenicity and inhibited autophagy. Mechanistic studies showed that USP12 interacted with, deubiquitylated and stabilized the critical autophagy mediator HMGB1 (high mobility group box-1) protein. Knockdown of USP12 decreased the level of HMGB1 and suppressed HMGB1-mediated autophagy in MM. Furthermore, basal autophagy activity associated with USP12/HMGB1 was elevated in bortezomib (BTZ)-resistant MM cell lines. USP12 depletion, concomitant with a reduced expression of HMGB1, suppressed autophagy and increased the sensitivity of resistant cells to BTZ. Collectively, our findings have identified an important role of the deubiquitylase USP12 in pro-survival autophagy and resultant BTZ resistance in MM by stabilizing HMGB1, suggesting that the USP12/HMGB1 axis might be pursued as a potential diagnostic and therapeutic target in human MM.
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