ArticleBlood2020
Myeloid cell-targeted miR-146a mimic inhibits NF-κB-driven inflammation and leukemia progression in vivo.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
- Recent trends in research on the role of cholesterol in leukemia: a bibliometric and visualization study.Frontiers in immunology · 2025Pooled it
- Decreased serum levels of the inflammaging marker miR-146a are associated with clinical non-response to tocilizumab in COVID-19 patients.Mechanisms of ageing and development · 2021Trial
- miR-146a mimic therapy protects against platelet-mediated thrombosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- A pH-responsive miR-146a-loaded Gel/MSN nanocarrier enhances anti-inflammatory efficacy in allergic rhinitis through pyroptosis suppression.Journal of translational medicine · 2026Article
- A novel endosome-escaping, macrophage-targeted nanoparticle platform for miR-146a delivery with favorable in vivo biodistribution and biocompatibility.bioRxiv : the preprint server for biology · 2026Article
- Endosome-escaping engineered LNP-miR146a with in vivo biodistribution to mitigate inflammation and foreign body giant cell formation.bioRxiv : the preprint server for biology · 2026Article
- MicroRNAs in Long COVID: Key Regulators, Biomarkers, and Therapeutic Targets of Post-SARS-CoV-2 Sequelae.Biomolecules · 2026Review
- The structure and functions of TRAF families and recent advances of TRAFs in leukemia.Frontiers in oncology · 2026Review
- The miRNA Landscape of Leukemia - Cellular Actions to Therapy through Molecular Mechanisms.Cell biochemistry and biophysics · 2025Review
- RNA Therapeutics in Heart Failure.Journal of cardiovascular translational research · 2025Review
- Reflecting on 30 years of miRNA biology in malignant hematology: current challenges and future directions.Blood advances · 2025Review
- Cell-selective telomere damage by thiopurine-based oligonucleotide for diffuse large B cell lymphoma immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Exploring the therapeutic potential of MSC-derived secretomes in neonatal care: focus on BPD and NEC.Stem cell research & therapy · 2025Review
- Redesigning miR-34a: structural and chemical advances in the therapeutic development of an miRNA anti-cancer agent.Biochemical Society transactions · 2025Article
- Unleashing the TLR9-driven multilineage differentiation of myeloid leukemia cellsMolecular therapy. Nucleic acids · 2025Article
- MiR-146a Reduces Inflammation in Experimental Pancreatitis via the TRAF6-NF-κB Signaling Pathway in Mice.Immunity, inflammation and disease · 2025Article
- Macrophage microRNA-146a is a central regulator of the foreign body response to biomaterial implants.Biomaterials · 2025Article
- Cellular Phenotypic Transformation During Atherosclerosis: The Potential Role of miRNAs as Biomarkers.International journal of molecular sciences · 2025Review
- miR-142 deficit in T cells during blast crisis promotes chronic myeloid leukemia immune escape.Nature communications · 2025Article
- Regulation of innate immune response by miRNAs up-regulated in Stevens-Johnson syndrome with severe ocular complications.Scientific reports · 2025Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
NF-κB is a key regulator of inflammation and cancer progression, with an important role in leukemogenesis. Despite its therapeutic potential, targeting NF-κB using pharmacologic inhibitors has proven challenging. Here, we describe a myeloid cell-selective NF-κB inhibitor using an miR-146a mimic oligonucleotide conjugated to a scavenger receptor/Toll-like receptor 9 agonist (C-miR146a). Unlike an unconjugated miR146a, C-miR146a was rapidly internalized and delivered to the cytoplasm of target myeloid cells and leukemic cells. C-miR146a reduced expression of classic miR-146a targets (IRAK1 and TRAF6), thereby blocking activation of NF-κB in target cells. IV injections of C-miR146a mimic to miR-146a-deficient mice prevented excessive NF-κB activation in myeloid cells, and thus alleviated myeloproliferation and mice hypersensitivity to bacterial challenge. Importantly, C-miR146a showed efficacy in dampening severe inflammation in clinically relevant models of chimeric antigen receptor (CAR) T-cell-induced cytokine release syndrome. Systemic administration of C-miR146a oligonucleotide alleviated human monocyte-dependent release of IL-1 and IL-6 in a xenotransplanted B-cell lymphoma model without affecting CD19-specific CAR T-cell antitumor activity. Beyond anti-inflammatory functions, miR-146a is a known tumor suppressor commonly deleted or expressed at reduced levels in human myeloid leukemia. Using The Cancer Genome Atlas acute myeloid leukemia data set, we found an inverse correlation of miR-146a levels with NF-κB-related genes and with patient survival. Correspondingly, C-miR146a induced cytotoxic effects in human MDSL, HL-60, and MV4-11 leukemia cells in vitro. The repeated IV administration of C-miR146a inhibited expression of NF-κB target genes and thereby thwarted progression of disseminated HL-60 leukemia. Our results show the potential of using myeloid cell-targeted miR-146a mimics for the treatment of inflammatory and myeloproliferative disorders.
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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.