ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023
Smoking-Induced M2-TAMs, via circEML4 in EVs, Promote the Progression of NSCLC through ALKBH5-Regulated m6A Modification of SOCS2 in NSCLC Cells.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
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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
56 citing papers in PubMed, 66 citations in OpenAlex.
- Exosomal circular RNAs in the tumor immune microenvironment: From regulatory mechanisms to therapeutic opportunities and translational hurdles (Review).International journal of molecular medicine · 2026Review
- Tumor-Derived Exosomal circAP2B1 Induces M2 Macrophage Polarization by Enhancing Mitochondrial Homeostasis to Promote Esophageal Squamous Cell Carcinoma Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- RNA modifications in intestinal macrophages: Implications for gut immunity and inflammation.Genes & diseases · 2026Review
- Multi-omics and network pharmacology identify IGFBP1 as an m6A-Epigenetic target of pueraria in NSCLC therapy.PLoS computational biology · 2026Article
- Emerging Dual Roles of ALKBH5 in Ischemia-reperfusion Injury: Mechanisms and Therapeutic Implications.Cell biochemistry and biophysics · 2026Review
- HMGB1 as Double-Edged Regulator of Cancer Therapy: Mechanistic Roles in Chemotherapy Resistance and Immunotherapy Response.OncoTargets and therapy · 2026Review
- Roles of Cellular Neighborhoods in Lung Cancer.Journal of Cancer · 2026Review
- Context-dependent functions of ALKBH5: a mechanistic framework linking cellular stress responses, immune regulation, viral infection, and therapeutic vulnerabilities.Frontiers in immunology · 2026Review
- Emerging functions of m6A-modified circRNAs and their targeting strategies in lung cancer.Frontiers in cell and developmental biology · 2026Review
- Polarization-Specific Macrophage-Derived Extracellular Vesicles: Molecular Cargo, Tumor Microenvironment Remodeling, and Therapeutic Opportunities.International journal of nanomedicine · 2026Review
- RNA modifications: roles in immune cell biology and tumor regulation.Cancer cell international · 2025Review
- Fucosyltransferase 8-Derived Circular RNA Drives M2 Polarization of Macrophages Through ENO1-TNF Signaling Axis to Promote Lung Cancer Progression.Thoracic cancer · 2025Article
- CircRNA in non‑small cell lung cancer: Potential biomarkers and therapeutic targets (Review).Molecular medicine reports · 2025Review
- Comprehensive evaluation of risk factors for LNM and distant metastasis in patients with NSCLC.Scientific reports · 2025Article
- N6-methyladenosine-modified circDCP2 promotes carbon black nanoparticle-induced malignancy in human bronchial epithelial cells via PI3K-AKT pathway and macrophage homeostasis.Journal of nanobiotechnology · 2025Article
- A game of hide-and-seek: how extracellular vesicles evade the immune system.Drug delivery and translational research · 2025Review
- ADAR1-HNRNPL-Mediated CircCANX Decline Promotes Autophagy in Chronic Obstructive Pulmonary Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- M2 macrophage-derived exosomes promote cell proliferation, migration and EMT of non-small cell lung cancer by secreting miR-155-5p.Molecular and cellular biochemistry · 2025Article
- Suppressor of cytokine signaling 2 modulates regulatory T cell activity to suppress liver hepatocellular carcinoma growth and metastasis.World journal of gastroenterology · 2025Article
- Effects of circulating RNAs on tumor metabolism in lung cancer (Review).Oncology letters · 2025Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Lung cancer is a commonly diagnosed disease worldwide, with non-small cell lung cancers (NSCLCs) accounting for ≈ 85% of cases. Cigarette smoke is an environmental exposure promoting progression of NSCLC, but its role is poorly understood. This study reports that smoking-induced accumulation of M2-type tumor-associated macrophages (M2-TAMs) surrounding NSCLC tissues promotes malignancy. Specifically, extracellular vesicles (EVs) from cigarette smoke extract (CSE)-induced M2 macrophages promoted malignancy of NSCLC cells in vitro and in vivo. circEML4 in EVs from CSE-induced M2 macrophages is transported to NSCLC cells, where it reduced the distribution of ALKBH5 in the nucleus by interacting with Human AlkB homolog H5 (ALKBH5), resulting in elevated N6-methyladenosine (m6A) modifications. m6A-seq and RNA-seq revealed suppressor of cytokine signaling 2 (SOCS2)-mediated activation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway by regulating m6A modification of SOCS2 via ALKBH5. Down-regulation of circEML4 in EVs from CSE-induced M2 macrophages reversed EVs-enhanced tumorigenicity and metastasis in NSCLC cells. Furthermore, this study found that smoking patients showed an increase in circEML4-positive M2-TAMs. These results indicate that smoking-induced M2-TAMs via circEML4 in EVs promote the NSCLC progression through ALKBH5-regulated m6A modification of SOCS2. This study also reveals that circEML4 in EVs from TAMs acts as a diagnostic biomarker for NSCLC, especially for patients with smoking history.
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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.