Hypoxic glioma-derived exosomes deliver microRNA-1246 to induce M2 macrophage polarization by targeting TERF2IP via the STAT3 and NF-κB pathways
Abstract
Exosomes are emerging as important elements that participate in intercellular communication and tumor microenvironment modulation, but the exact mechanisms by which tumor exosomes facilitate the generation of the immunosuppressive microenvironment remain unclear. Here we investigated the effects of glioma-derived exosomes (GDEs) on macrophage polarization and glioma progression. We also performed microRNA sequencing analysis of GDEs to identify the microRNA that mediated macrophage polarization. The microRNA-associated intracellular signaling pathway in macrophages was further investigated. Compared with normoxic glioma-derived exosomes (N-GDEs), hypoxic glioma-derived exosomes (H-GDEs) markedly induced M2 macrophage polarization, which subsequently promoted glioma proliferation, migration and invasion in vitro and in vivo. MicroRNA sequencing analysis identified miR-1246 as the most enriched microRNA in H-GDEs. Moreover, miR-1246 was enriched in the CSF of GBM patients and decreased after tumor resection. Further investigation determined that miR-1246 mediated H-GDE-induced M2 macrophage polarization by targeting TERF2IP to activate the STAT3 signaling pathway and inhibit the NF-κB signaling pathway. Our study elucidated a mechanism by which hypoxia and glioma influence M2 macrophage polarization via exosomes, which could facilitate the formation of the immunosuppressive microenvironment. Moreover, our results suggested that miR-1246 in the CSF of GBM patients may be a novel…
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miR-1246 induces M2 macrophage polarization by targeting TERF2IP via the STAT3 and NF-κB pathways.
“Qian et al. documented another microRNA, miR-1246, which induces M2 macrophage polarization by targeting TERF2IP via the STAT3 and NF-κB pathways [182].”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [182]
Cites
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“Hypoxic glioma cells secrete sEVs containing miR-1246 to induce the M2 phenotype in macrophages (13).”
BackgroundSelf-citationMicroRNAs as Regulators of Phagocytosis
Gierlikowski, W., & Gierlikowska, B. (2022) · Cells · doi:10.3390/cells11091380 · Cited by 25 · see citing works
- Authors
- Qian, M., Wang, S., Guo, X., Wang, J., Zhang, Z., Qiu, W., Gao, X., Chen, Z., Xu, J., Zhao, R., Xue, H., & Li, G.
- Affiliations
- Shandong University (CN)
- Corresponding author
- Xue, Hao
- Li, Gang
- ORCID
- Venue
- Oncogene
- Published
- 2019-09-04
- Volume
- 39
- Issue
- 2
- Pages
- 428-442
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2972185292
- Cited by
- 345
- References
- 4
- Citations by year
- 2026: 26 · 2025: 38 · 2024: 71 · 2023: 50 · 2022: 75 · 2021: 55 · 2020: 28 · 2019: 2
- FWCI
- 13.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (30872645, 81372719, 81172403, 81571284, 91542115, 81874083, 81702468)
- Natural Science Foundation of Shandong Province (2017CXGC1203, 2013GGE27006, 2017G006012)
- Taishan Scholar Foundation of Shandong Province (ts201511093)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Keywords
- hypoxia, M2 macrophage polarization, STAT3 signaling, NF-κB signaling, glioblastoma, tumor microenvironment, immunosuppressive microenvironment, glioma progression, cerebrospinal fluid biomarkers, glioma diagnosis, cancer immunotherapy
- MeSH terms
- Tumor Hypoxia, Shelterin Complex, Glioma, Humans, Macrophages, Phagocytosis, Signal Transduction, NF-kappa B, Telomere-Binding Proteins, MicroRNAs, Cell Line, Tumor, STAT3 Transcription Factor, Exosomes
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