ArticleCancer medicine2018
ARNT/HIF-1β links high-risk 1q21 gain and microenvironmental hypoxia to drug resistance and poor prognosis in multiple myeloma.
Article in Cancer medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- Proteomic profiling revealed unique disease biology associated with 1q abnormalities in multiple myeloma.NPJ precision oncology · 2026Article
- Concordant Shared Transcriptomic Signatures and Candidate Regulatory Features in Chronic Lymphocytic Leukemia and Multiple Myeloma.Oncology research · 2026Article
- Carfilzomib resistance in multiple myeloma: A comparative metabolomic analysis.Journal of applied genetics · 2025Article
- Decoding NF-κB: nucleocytoplasmic shuttling dynamics, synthetic modulation and post-therapeutic behavior in cancer.Molecular biology reports · 2025Review
- A new autophagy-related nomogram and mechanism in multiple myeloma.Genes & diseases · 2024Article
- The numerous facets of 1q21Oncology letters · 2024Review
- Targeting ARNT attenuates chemoresistance through destabilizing p38α-MAPK signaling in glioblastoma.Cell death & disease · 2024Article
- Immunomodulatory properties of CD38 antibodies and their effect on anticancer efficacy in multiple myeloma.Cancer medicine · 2023Review
- Article
- AhR and HIF-1International journal of cell biology · 2023Article
- The signaling pathway of hypoxia inducible factor in regulating gut homeostasis.Frontiers in microbiology · 2023Review
- An mTORC1 to HRI signaling axis promotes cytotoxicity of proteasome inhibitors in multiple myeloma.Cell death & disease · 2022Article
- Single-cell transcriptomics of neuroblastoma identifies chemoresistance-associated genes and pathways.Computational and structural biotechnology journal · 2022Article
- Hypoxia-inducible factor-1β is essential for upregulation of the hypoxia-induced FLT1 gene in placental trophoblasts.Molecular human reproduction · 2021Article
- Chronic and Cycling Hypoxia: Drivers of Cancer Chronic Inflammation through HIF-1 and NF-κB Activation: A Review of the Molecular Mechanisms.International journal of molecular sciences · 2021Review
- Chromatin Accessibility Identifies Regulatory Elements Predictive of Gene Expression and Disease Outcome in Multiple Myeloma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Hypoxia-Induced Non-Coding RNAs Controlling Cell Viability in Cancer.International journal of molecular sciences · 2021Review
- Review
- Treatment Strategies Considering Micro-Environment and Clonal Evolution in Multiple Myeloma.Cancers · 2021Review
- Identification and expression profile of microRNA in seven tissues of the Golden snub-nosed monkey (Rhinopithecus roxellanae).Molecular genetics and genomics : MGG · 2020Article
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
1q21 gain is a common cytogenetic abnormality featuring high-risk multiple myeloma (HRMM). However, the molecular mechanism underlying the adverse prognostic effect of 1q21 gain remains largely unclear. Here, we report that ARNT/HIF-1β, a 1q21 gene, is highly expressed in HRMM and induced by microenvironmental hypoxia, which confers drug resistance and correlates with inferior outcome. Analysis of the gene expression profile database revealed that ARNT expression was upregulated in MM and increased with disease progression or in HRMM subtypes (particularly 1q21 gain), while correlated to shorter overall survival. In a cohort of 40 MM patients, qPCR further validated that ARNT expression was higher in MM patients than normal donors. MM cells carrying 1q21 gain or acquired drug resistance displayed a robust increase in HIF-1β protein level. Hypoxia induced HIF-1β expression via a NF-κB-dependent process. Notably, HIF-1β overexpression impaired bortezomib sensitivity, whereas shRNA knockdown of ARNT reversed hypoxia-mediated drug resistance. Together, these findings suggest that ARNT/HIF-1β might represent a novel biomarker for risk stratification and prognosis of HRMM patients, as well as a potential therapeutic target for overcoming 1q21 gain- or microenvironment-mediated and acquired drug resistance in MM.
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