ArticleOncogene2017
PU.1 acts as tumor suppressor for myeloma cells through direct transcriptional repression of IRF4.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Pharmacological targeting of IRF4 as a therapeutic strategy for multiple myeloma.Nature chemical biology · 2026Article
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- Decoding multiple myeloma: single-cell insights into tumor heterogeneity, immune dynamics, and disease progression.Frontiers in immunology · 2025Article
- CRISPRi screens identify the lncRNA,Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- LINC00998 Modulating M2 Macrophage Activation in Allergic Rhinitis by Stabilizing BOB.1 mRNA.Journal of inflammation research · 2024Article
- Resolving therapy resistance mechanisms in multiple myeloma by multiomics subclone analysis.Blood · 2023Article
- ANP32B suppresses B-cell acute lymphoblastic leukemia through activation of PU.1 in mice.Cancer science · 2023Article
- SUMOylation inhibition enhances multiple myeloma sensitivity to lenalidomide.Cancer gene therapy · 2023Article
- Macrophage-targeted delivery of siRNA to silenceBioengineering & translational medicine · 2022Article
- Understanding the Crosstalk Between Epigenetics and Immunometabolism to Combat Cancer.Sub-cellular biochemistry · 2022Article
- Overexpression of long non-coding RNA WT1-AS or silencing of PIK3AP1 are inhibitory to cervical cancer progression.Cell cycle (Georgetown, Tex.) · 2021Article
- The complex relationship between MITF and the immune system: a Melanoma ImmunoTherapy (response) Factor?Molecular cancer · 2020Review
- Che-1/AATF-induced transcriptionally active chromatin promotes cell proliferation in multiple myeloma.Blood advances · 2020Article
- Transcriptional, Epigenetic and Metabolic Programming of Tumor-Associated Macrophages.Cancers · 2020Review
- "Amyloid-beta accumulation cycle" as a prevention and/or therapy target for Alzheimer's disease.Aging cell · 2020Review
- Down-regulation and clinical significance of miR-7-2-3p in papillary thyroid carcinoma with multiple detecting methods.IET systems biology · 2019Article
- Metabolic, Anti-apoptotic and Immune Evasion Strategies of Primary Human Myeloma Cells Indicate Adaptations to Hypoxia.Molecular & cellular proteomics : MCP · 2019Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We previously reported that PU.1 is downregulated in the majority of myeloma cell lines and primary myeloma cells of certain myeloma patients, and conditional expression of PU.1 in such myeloma cell lines induced cell cycle arrest and apoptosis. We found downregulation of IRF4 protein in the U266 myeloma cell line following induction of PU.1. Previous studies reported that knockdown of IRF4 in myeloma cell lines induces apoptosis, prompting us to further investigate the role of IRF4 downregulation in PU.1-induced cell cycle arrest and apoptosis in myeloma cells. PU.1 induced downregulation of IRF4 at the protein level, cell cycle arrest and apoptosis in six myeloma cell lines. Chromatin immunoprecipitation (ChIP) revealed that PU.1 directly binds to the IRF4 promoter, whereas a reporter assay showed that PU.1 may suppress IRF4 promoter activity. Stable expression of IRF4 in myeloma cells expressing PU.1 partially rescued the cells from apoptosis induced by PU.1. As it was reported that IRF4 directly binds to the IRF7 promoter and downregulates its expression in activated B cell-like subtype of diffuse large B cell lymphoma cells, we performed ChIP assays and found that IRF4 directly binds the IRF7 promoter in myeloma cells. It is known that IRF7 positively upregulates interferon-β (IFNβ) and induces apoptosis in many cell types. Binding of IRF4 to the IRF7 promoter decreased following PU.1 induction, accompanied by downregulation of IRF4 protein expression. Knockdown of IRF7 protected PU.1-expressing myeloma cells from apoptosis. Furthermore, IFNβ, which is a downstream target of IRF7, was upregulated in myeloma cells along with IRF7 after PU.1 induction. Finally, we evaluated the mRNA expression levels of PU.1, IRF4 and IRF7 in primary myeloma cells from patients and found that PU.1 and IRF7 were strongly downregulated in contrast to the high expression levels of IRF4. These data strongly suggest that PU.1-induced apoptosis in myeloma cells is associated with IRF4 downregulation and subsequent IRF7 upregulation.
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