ArticleCell death & disease2021
Hypoxic stress suppresses lung tumor-secreted exosomal miR101 to activate macrophages and induce inflammation.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 25 citations in OpenAlex.
- Engineering exosomes with iRGD for targeted RNAi therapy against pancreatic cancer mediated by long non-coding RNA PLBD1-AS1.PloS one · 2026Article
- miRNA101a secreted by EATMs regulates atrial fibrillation through the PDGF-mediated PI3K/AKT pathway.Frontiers in pharmacology · 2026Article
- Tumor microenvironment-induced epigenetic reprogramming of Tregs and its impact on immunotherapy.Frontiers in genetics · 2026Review
- CDK8 mediated inflammatory microenvironment aggravates osteoarthritis progression.Journal of advanced research · 2025Article
- Exosome-based approaches in cancer along with unlocking new insights into regeneration of cancer-prone tissues.Regenerative therapy · 2025Review
- Tumor-associated macrophages remodel the suppressive tumor immune microenvironment and targeted therapy for immunotherapy.Journal of experimental & clinical cancer research : CR · 2025Review
- Myeloid Mir34a suppresses colitis-associated colon cancer: characterization of mediators by single-cell RNA sequencing.Cell death and differentiation · 2025Article
- Decoding the Tumor Microenvironment: Exosome-Mediated Macrophage Polarization and Therapeutic Frontiers.International journal of biological sciences · 2025Review
- Knockdown ofFrontiers in pharmacology · 2024Article
- Hypoxia-Driven Changes in Tumor Microenvironment: Insights into Exosome-Mediated Cell Interactions.International journal of nanomedicine · 2024Review
- The Role of Exosome-Derived microRNA on Lung Cancer Metastasis Progression.Biomolecules · 2023Review
- The therapeutic potential of exosomes in lung cancer.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- Exosomal Non-Coding RNAs: Novel Regulators of Macrophage-Linked Intercellular Communication in Lung Cancer and Inflammatory Lung Diseases.Biomolecules · 2023Review
- Review
- Tumor Cell-derived Extracellular Vesicles in Modulating Phenotypes and Immune Functions of Macrophages: Mechanisms and Therapeutic Applications.Journal of Cancer · 2023Review
- The hypoxia-driven crosstalk between tumor and tumor-associated macrophages: mechanisms and clinical treatment strategies.Molecular cancer · 2022Review
- The Extracellular MicroRNAs on Inflammation: A Literature Review of Rodent Studies.Biomedicines · 2022Review
- Exosomes in the hypoxic TME: from release, uptake and biofunctions to clinical applications.Molecular cancer · 2022Review
- Tumor-derived extracellular vesicles modulate innate immune responses to affect tumor progression.Frontiers in immunology · 2022Review
- Hypoxia Induced Changes of Exosome Cargo and Subsequent Biological Effects.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia promotes inflammation in the tumor microenvironment. Although hypoxia-inducible factor 1α (HIF1α) is a master modulator of the response to hypoxia, the exact mechanisms through which HIF1α regulates the induction of inflammation remain largely unclear. Using The Cancer Genome Atlas Lung Squamous Cell Carcinoma (TCGA-LUSC) database, we divided patients with LUSC into two groups based on low or high HIF1α expression. After analyzing the differentially expressed genes in these two groups, we found that HIF1α was positively correlated with interleukin 1A (IL1A) and IL6 expression. Our in vitro study showed that hypoxic stress did not induce IL1A or IL6 expression in tumor cells or macrophages but dramatically enhanced their expression when co-cultured with tumor cells. We then investigated the effect of tumor-derived exosomes on macrophages. Our data suggested that the changes in miR101 in the tumor-derived exosomes played an important role in IL1A and IL6 expression in macrophages, although the hypoxic stress did not change the total amount of exosome secretion. The expression of miR101 in exosomes was suppressed by hypoxic stress, since depletion of HIF1α in tumor cells recovered the miR101 expression in both tumor cells and exosomes. In vitro, miRNA101 overexpression or uptake enriched exosomes by macrophages suppressed their reprogramming into a pro-inflammatory state by targeting CDK8. Injection of miR101 into xenografted tumors resulted in the suppression of tumor growth and macrophage tumor infiltration in vivo. Collectively, this study suggests that the HIF1α-dependent suppression of exosome miR101 from hypoxic tumor cells activates macrophages to induce inflammation in the tumor microenvironment.
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