{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:10:05Z","timestamp":1792800605406,"version":"4.5.0"},"reference-count":71,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T00:00:00Z","timestamp":1729036800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T00:00:00Z","timestamp":1729036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"The Special Foundation for Taishan Scholars","award":["tshw201502056"],"award-info":[{"award-number":["tshw201502056"]}]},{"name":"The Department of Science & Technology of Shandong Province","award":["ZR2019ZD33"],"award-info":[{"award-number":["ZR2019ZD33"]}],"id":[{"id":"https:\/\/ror.org\/01b9fvd84","id-type":"ROR","asserted-by":"crossref"}]},{"name":"The Clinical Research Center of Shandong University","award":["2020SDUCRCB002"],"award-info":[{"award-number":["2020SDUCRCB002"]}]},{"name":"Shandong Provincial Laboratory Project","award":["SYS202202, JNL-2022003A"],"award-info":[{"award-number":["SYS202202, JNL-2022003A"]}]},{"name":"Shandong Provincial Laboratory Project","award":["SYS202202, JNL-2022042C"],"award-info":[{"award-number":["SYS202202, JNL-2022042C"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82203760"],"award-info":[{"award-number":["82203760"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Nanobiotechnol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Exosomes (EXO) play crucial roles in intercellular communication and glioma microenvironment modulation. Tumor-associated macrophages are more likely to become M2-like type macrophages in the immunosuppressive microenvironment. Here, we aimed to investigate the effects and molecular mechanisms of hypoxic glioma-derived exosomes mediated M2-like macrophage polarization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Highly expressed miRNAs in exosomes derived from glioma cells cultured under hypoxia condition compared to normoxic condition were identified through microRNA sequencing. The polarization status of macrophages was determined using qRT-PCR, Western blotting, flow cytometry, and immunohistochemistry. By using RNA-seq, we aimed to identify the downstream target genes regulated by miR-25-3p in macrophages and investigate the mechanistic pathways through which it exerts its effects. The proliferation and migration capabilities of glioma cells were assessed through EdU, Transwell assays, and in vivo experiments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that miR-25-3p was upregulated in the exosomes derived from hypoxic glioma cells and can be transferred to the macrophage. In macrophages, miR-25-3p downregulates the expression of PHLPP2, thereby activating the PI3K-AKT-mTOR signaling pathway, ultimately leading to macrophage M2 polarization. As part of a feedback loop, M2-polarized macrophages can, in turn, promote malignant glioma progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study reveals that miR-25-3p from hypoxic glioma cells is delivered to macrophages via exosomes as a mediator, promoting M2 polarization of macrophages through the miR-25-3p\/PHLPP2\/PI3K-AKT signaling pathway. This study suggests that targeted interventions to modulate miR-25-3p expression, transmission, or inhibition of PI3K-AKT pathway activation can disrupt the immune-suppressive microenvironment, providing a novel approach for immunotherapy in gliomas.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s12951-024-02888-5","type":"journal-article","created":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T22:01:41Z","timestamp":1729029701000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Hypoxic glioma-derived exosomal miR-25-3p promotes macrophage M2 polarization by activating the PI3K-AKT-mTOR signaling pathway"],"prefix":"10.1186","volume":"22","author":[{"given":"Zhiwei","family":"Xue","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junzhi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenchen","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiyu","family":"Mu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanzhao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangli","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuchen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiwei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,16]]},"reference":[{"issue":"21","key":"2888_CR1","doi-asserted-by":"publisher","first-page":"2683","DOI":"10.1101\/gad.1596707","volume":"21","author":"FB Furnari","year":"2007","unstructured":"Furnari FB, Fenton T, Bachoo RM, Mukasa A, Stommel JM, Stegh A, Hahn WC, Ligon KL, Louis DN, Brennan C, et al. Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev. 2007;21(21):2683\u2013710.","journal-title":"Genes Dev"},{"issue":"10","key":"2888_CR2","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1056\/NEJMoa043330","volume":"352","author":"R Stupp","year":"2005","unstructured":"Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987\u201396.","journal-title":"N Engl J Med"},{"issue":"23","key":"2888_CR3","doi-asserted-by":"publisher","first-page":"2306","DOI":"10.1001\/jama.2017.18718","volume":"318","author":"R Stupp","year":"2017","unstructured":"Stupp R, Taillibert S, Kanner A, Read W, Steinberg D, Lhermitte B, Toms S, Idbaih A, Ahluwalia MS, Fink K, et al. Effect of Tumor-Treating Fields Plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a Randomized Clinical Trial. JAMA. 2017;318(23):2306\u201316.","journal-title":"JAMA"},{"issue":"15","key":"2888_CR4","doi-asserted-by":"publisher","first-page":"3012","DOI":"10.4161\/cc.9.15.12710","volume":"9","author":"N Charles","year":"2010","unstructured":"Charles N, Holland EC. The perivascular niche microenvironment in brain tumor progression. Cell Cycle (Georgetown Tex). 2010;9(15):3012\u201321.","journal-title":"Cell Cycle (Georgetown Tex)"},{"issue":"6","key":"2888_CR5","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/j.ccr.2009.03.018","volume":"15","author":"Z Li","year":"2009","unstructured":"Li Z, Bao S, Wu Q, Wang H, Eyler C, Sathornsumetee S, Shi Q, Cao Y, Lathia J, McLendon RE, et al. Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell. 2009;15(6):501\u201313.","journal-title":"Cancer Cell"},{"key":"2888_CR6","doi-asserted-by":"crossref","unstructured":"Hao NB, L\u00fc MH, Fan YH, Cao YL, Zhang ZR, Yang SM. Macrophages in tumor microenvironments and the progression of tumors. Clinical & developmental immunology 2012, 2012:948098.","DOI":"10.1155\/2012\/948098"},{"issue":"11","key":"2888_CR7","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1038\/nm.3394","volume":"19","author":"DF Quail","year":"2013","unstructured":"Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med. 2013;19(11):1423\u201337.","journal-title":"Nat Med"},{"issue":"1","key":"2888_CR8","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1186\/s12974-018-1288-0","volume":"15","author":"C Dello Russo","year":"2018","unstructured":"Dello Russo C, Cappoli N, Coletta I, Mezzogori D, Paciello F, Pozzoli G, Navarra P, Battaglia A. The human microglial HMC3 cell line: where do we stand? A systematic literature review. J Neuroinflamm. 2018;15(1):259.","journal-title":"J Neuroinflamm"},{"issue":"12","key":"2888_CR9","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/j.it.2004.09.015","volume":"25","author":"A Mantovani","year":"2004","unstructured":"Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 2004;25(12):677\u201386.","journal-title":"Trends Immunol"},{"issue":"12","key":"2888_CR10","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1038\/nri1733","volume":"5","author":"S Gordon","year":"2005","unstructured":"Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol. 2005;5(12):953\u201364.","journal-title":"Nat Rev Immunol"},{"issue":"1","key":"2888_CR11","doi-asserted-by":"publisher","first-page":"444","DOI":"10.4049\/jimmunol.1103248","volume":"189","author":"XZ Ye","year":"2012","unstructured":"Ye XZ, Xu SL, Xin YH, Yu SC, Ping YF, Chen L, Xiao HL, Wang B, Yi L, Wang QL, et al. Tumor-associated microglia\/macrophages enhance the invasion of glioma stem-like cells via TGF-\u03b21 signaling pathway. J Immunol. 2012;189(1):444\u201353.","journal-title":"J Immunol"},{"issue":"3","key":"2888_CR12","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1101\/gad.294348.116","volume":"31","author":"X Guo","year":"2017","unstructured":"Guo X, Zhao Y, Yan H, Yang Y, Shen S, Dai X, Ji X, Ji F, Gong XG, Li L, et al. Single tumor-initiating cells evade immune clearance by recruiting type II macrophages. Genes Dev. 2017;31(3):247\u201359.","journal-title":"Genes Dev"},{"issue":"5","key":"2888_CR13","first-page":"648","volume":"19","author":"C Zhu","year":"2017","unstructured":"Zhu C, Mustafa D, Zheng PP, van der Weiden M, Sacchetti A, Brandt M, Chrifi I, Tempel D, Leenen PJM, Duncker DJ, et al. Activation of CECR1 in M2-like TAMs promotes paracrine stimulation-mediated glial tumor progression. Neuro Oncol. 2017;19(5):648\u201359.","journal-title":"Neuro Oncol"},{"issue":"2","key":"2888_CR14","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1158\/2326-6066.CIR-18-0145","volume":"7","author":"J Cao","year":"2019","unstructured":"Cao J, Dong R, Jiang L, Gong Y, Yuan M, You J, Meng W, Chen Z, Zhang N, Weng Q, et al. LncRNA-MM2P identified as a modulator of macrophage M2 polarization. Cancer Immunol Res. 2019;7(2):292\u2013305.","journal-title":"Cancer Immunol Res"},{"key":"2888_CR15","doi-asserted-by":"crossref","unstructured":"Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science (New York, NY) 2020, 367(6478).","DOI":"10.1126\/science.aau6977"},{"issue":"6","key":"2888_CR16","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1016\/j.cell.2016.01.043","volume":"164","author":"M Tkach","year":"2016","unstructured":"Tkach M, Th\u00e9ry C. Communication by Extracellular vesicles: where we are and where we need to go. Cell. 2016;164(6):1226\u201332.","journal-title":"Cell"},{"issue":"6","key":"2888_CR17","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1016\/j.ccell.2016.10.009","volume":"30","author":"A Becker","year":"2016","unstructured":"Becker A, Thakur BK, Weiss JM, Kim HS, Peinado H, Lyden D. Extracellular vesicles in Cancer: cell-to-cell mediators of Metastasis. Cancer Cell. 2016;30(6):836\u201348.","journal-title":"Cancer Cell"},{"issue":"2","key":"2888_CR18","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1016\/j.cell.2019.02.029","volume":"177","author":"DK Jeppesen","year":"2019","unstructured":"Jeppesen DK, Fenix AM, Franklin JL, Higginbotham JN, Zhang Q, Zimmerman LJ, Liebler DC, Ping J, Liu Q, Evans R, et al. Reassessment of Exosome Composition. Cell. 2019;177(2):428\u2013e445418.","journal-title":"Cell"},{"issue":"1","key":"2888_CR19","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/s41419-022-04510-8","volume":"13","author":"W Tian","year":"2022","unstructured":"Tian W, Lei N, Zhou J, Chen M, Guo R, Qin B, Li Y, Chang L. Extracellular vesicles in ovarian cancer chemoresistance, metastasis, and immune evasion. Cell Death Dis. 2022;13(1):64.","journal-title":"Cell Death Dis"},{"issue":"6","key":"2888_CR20","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1038\/ncb1596","volume":"9","author":"H Valadi","year":"2007","unstructured":"Valadi H, Ekstr\u00f6m K, Bossios A, Sj\u00f6strand M, Lee JJ, L\u00f6tvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9(6):654\u20139.","journal-title":"Nat Cell Biol"},{"issue":"7","key":"2888_CR21","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1158\/0008-5472.CAN-15-1625","volume":"76","author":"L Li","year":"2016","unstructured":"Li L, Li C, Wang S, Wang Z, Jiang J, Wang W, Li X, Chen J, Liu K, Li C, et al. Exosomes derived from hypoxic oral squamous cell carcinoma cells deliver miR-21 to Normoxic Cells to Elicit a Prometastatic phenotype. Cancer Res. 2016;76(7):1770\u201380.","journal-title":"Cancer Res"},{"issue":"1","key":"2888_CR22","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1186\/s13046-022-02499-8","volume":"41","author":"S Qiu","year":"2022","unstructured":"Qiu S, Xie L, Lu C, Gu C, Xia Y, Lv J, Xuan Z, Fang L, Yang J, Zhang L, et al. Gastric cancer-derived exosomal miR-519a-3p promotes liver metastasis by inducing intrahepatic M2-like macrophage-mediated angiogenesis. J Exp Clin Cancer Res. 2022;41(1):296.","journal-title":"J Exp Clin Cancer Res"},{"issue":"7","key":"2888_CR23","doi-asserted-by":"publisher","first-page":"3183","DOI":"10.7150\/thno.52570","volume":"11","author":"Y Liang","year":"2021","unstructured":"Liang Y, Duan L, Lu J, Xia J. Engineering exosomes for targeted drug delivery. Theranostics. 2021;11(7):3183\u201395.","journal-title":"Theranostics"},{"key":"2888_CR24","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/j.jconrel.2022.05.027","volume":"347","author":"I Kimiz-Gebologlu","year":"2022","unstructured":"Kimiz-Gebologlu I, Oncel SS. Exosomes: large-scale production, isolation, drug loading efficiency, and biodistribution and uptake. J Control Release. 2022;347:533\u201343.","journal-title":"J Control Release"},{"issue":"1","key":"2888_CR25","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.cell.2018.03.006","volume":"173","author":"DP Bartel","year":"2018","unstructured":"Bartel DP. Metazoan MicroRNAs. Cell. 2018;173(1):20\u201351.","journal-title":"Cell"},{"issue":"1","key":"2888_CR26","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1101\/gr.082701.108","volume":"19","author":"RC Friedman","year":"2009","unstructured":"Friedman RC, Farh KK, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009;19(1):92\u2013105.","journal-title":"Genome Res"},{"issue":"3","key":"2888_CR27","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1002\/emmm.201100209","volume":"4","author":"MV Iorio","year":"2012","unstructured":"Iorio MV, Croce CM. MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol Med. 2012;4(3):143\u201359.","journal-title":"EMBO Mol Med"},{"key":"2888_CR28","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.ebiom.2016.09.017","volume":"12","author":"MY Shah","year":"2016","unstructured":"Shah MY, Ferrajoli A, Sood AK, Lopez-Berestein G, Calin GA. microRNA therapeutics in Cancer - An Emerging Concept. EBioMedicine. 2016;12:34\u201342.","journal-title":"EBioMedicine"},{"issue":"3","key":"2888_CR29","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/nrd.2016.246","volume":"16","author":"R Rupaimoole","year":"2017","unstructured":"Rupaimoole R, Slack FJ. MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov. 2017;16(3):203\u201322.","journal-title":"Nat Rev Drug Discov"},{"issue":"1","key":"2888_CR30","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s13046-019-1059-5","volume":"38","author":"L Zhang","year":"2019","unstructured":"Zhang L, Liao Y, Tang L. MicroRNA-34 family: a potential tumor suppressor and therapeutic candidate in cancer. J Exp Clin Cancer Res. 2019;38(1):53.","journal-title":"J Exp Clin Cancer Res"},{"issue":"1","key":"2888_CR31","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1186\/s13045-020-00991-2","volume":"13","author":"S Zhao","year":"2020","unstructured":"Zhao S, Mi Y, Guan B, Zheng B, Wei P, Gu Y, Zhang Z, Cai S, Xu Y, Li X, et al. Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer. J Hematol Oncol. 2020;13(1):156.","journal-title":"J Hematol Oncol"},{"issue":"9","key":"2888_CR32","doi-asserted-by":"publisher","first-page":"2102620","DOI":"10.1002\/advs.202102620","volume":"9","author":"Y Yin","year":"2022","unstructured":"Yin Y, Liu B, Cao Y, Yao S, Liu Y, Jin G, Qin Y, Chen Y, Cui K, Zhou L, et al. Colorectal Cancer-derived small extracellular vesicles promote Tumor Immune Evasion by upregulating PD-L1 expression in Tumor-Associated macrophages. Adv Sci (Weinh). 2022;9(9):2102620.","journal-title":"Adv Sci (Weinh)"},{"issue":"1","key":"2888_CR33","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s12943-024-01966-4","volume":"23","author":"C Deng","year":"2024","unstructured":"Deng C, Huo M, Chu H, Zhuang X, Deng G, Li W, Wei H, Zeng L, He Y, Liu H, et al. Exosome circATP8A1 induces macrophage M2 polarization by regulating the miR-1-3p\/STAT6 axis to promote gastric cancer progression. Mol Cancer. 2024;23(1):49.","journal-title":"Mol Cancer"},{"issue":"16","key":"2888_CR34","doi-asserted-by":"publisher","first-page":"4586","DOI":"10.1158\/0008-5472.CAN-17-3841","volume":"78","author":"X Wang","year":"2018","unstructured":"Wang X, Luo G, Zhang K, Cao J, Huang C, Jiang T, Liu B, Su L, Qiu Z. Hypoxic tumor-derived exosomal miR-301a mediates M2 macrophage polarization via PTEN\/PI3K\u03b3 to promote pancreatic Cancer metastasis. Cancer Res. 2018;78(16):4586\u201398.","journal-title":"Cancer Res"},{"key":"2888_CR35","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.canlet.2020.01.005","volume":"474","author":"D Wang","year":"2020","unstructured":"Wang D, Wang X, Si M, Yang J, Sun S, Wu H, Cui S, Qu X, Yu X. Exosome-encapsulated miRNAs contribute to CXCL12\/CXCR4-induced liver metastasis of colorectal cancer by enhancing M2 polarization of macrophages. Cancer Lett. 2020;474:36\u201352.","journal-title":"Cancer Lett"},{"key":"2888_CR36","doi-asserted-by":"crossref","unstructured":"Hu Y, Yuan M, Cheng L, Xu L, Wang G. Extracellular vesicle-encapsulated mir-25-3p promotes epithelial-mesenchymal transition and migration of endometrial epithelial cells by inducing macrophage polarization. Mol Hum Reprod 2024, 30(4): 1-17.","DOI":"10.1093\/molehr\/gaae010"},{"issue":"1\u20132","key":"2888_CR37","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/s11010-015-2516-x","volume":"409","author":"G Peng","year":"2015","unstructured":"Peng G, Yuan X, Yuan J, Liu Q, Dai M, Shen C, Ma J, Liao Y, Jiang W. miR-25 promotes glioblastoma cell proliferation and invasion by directly targeting NEFL. Mol Cell Biochem. 2015;409(1\u20132):103\u201311.","journal-title":"Mol Cell Biochem"},{"key":"2888_CR38","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.biopha.2015.02.005","volume":"71","author":"J Zhang","year":"2015","unstructured":"Zhang J, Gong X, Tian K, Chen D, Sun J, Wang G, Guo M. miR-25 promotes glioma cell proliferation by targeting CDKN1C. Biomed Pharmacotherapy = Biomedecine Pharmacotherapie. 2015;71:7\u201314.","journal-title":"Biomed Pharmacotherapy = Biomedecine Pharmacotherapie"},{"issue":"3","key":"2888_CR39","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1111\/j.1750-3639.2009.00328.x","volume":"20","author":"B Malzkorn","year":"2010","unstructured":"Malzkorn B, Wolter M, Liesenberg F, Grzendowski M, St\u00fchler K, Meyer HE, Reifenberger G. Identification and functional characterization of microRNAs involved in the malignant progression of gliomas. Brain Pathol. 2010;20(3):539\u201350.","journal-title":"Brain Pathol"},{"key":"2888_CR40","doi-asserted-by":"publisher","first-page":"729137","DOI":"10.3389\/fonc.2021.729137","volume":"11","author":"Z Yang","year":"2021","unstructured":"Yang Z, Gong W, Zhang T, Gao H. Molecular features of Glioma determined and validated using Combined TCGA and GTEx Data analyses. Front Oncol. 2021;11:729137.","journal-title":"Front Oncol"},{"issue":"5","key":"2888_CR41","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1038\/s41419-022-04908-4","volume":"13","author":"L Shi","year":"2022","unstructured":"Shi L, Cao Y, Yuan W, Guo J, Sun G. Exosomal circRNA BTG2 derived from RBP-J overexpressed-macrophages inhibits glioma progression via miR-25-3p\/PTEN. Cell Death Dis. 2022;13(5):506.","journal-title":"Cell Death Dis"},{"key":"2888_CR42","doi-asserted-by":"crossref","unstructured":"Wang J, Li T, Wang B. Exosomal transfer of miR\u201325\u20133p promotes the proliferation and temozolomide resistance of glioblastoma cells by targeting FBXW7. Int J Oncol 2021, 59(2): 1-15.","DOI":"10.3892\/ijo.2021.5244"},{"issue":"1","key":"2888_CR43","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1186\/s12964-024-01523-y","volume":"22","author":"S Tankov","year":"2024","unstructured":"Tankov S, Petrovic M, Lecoultre M, Espinoza F, El-Harane N, Bes V, Chliate S, Bedoya DM, Jordan O, Borchard G, et al. Hypoxic glioblastoma-cell-derived extracellular vesicles impair cGAS-STING activity in macrophages. Cell Communication Signaling: CCS. 2024;22(1):144.","journal-title":"Cell Communication Signaling: CCS"},{"issue":"1","key":"2888_CR44","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s12943-019-0981-7","volume":"18","author":"T Liu","year":"2019","unstructured":"Liu T, Zhang X, Du L, Wang Y, Liu X, Tian H, Wang L, Li P, Zhao Y, Duan W, et al. Exosome-transmitted mir-128-3p increase chemosensitivity of oxaliplatin-resistant colorectal cancer. Mol Cancer. 2019;18(1):43.","journal-title":"Mol Cancer"},{"issue":"2","key":"2888_CR45","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1038\/s41388-019-0996-y","volume":"39","author":"M Qian","year":"2020","unstructured":"Qian M, Wang S, Guo X, Wang J, Zhang Z, Qiu W, Gao X, Chen Z, Xu J, Zhao R, et al. Hypoxic glioma-derived exosomes deliver microRNA-1246 to induce M2 macrophage polarization by targeting TERF2IP via the STAT3 and NF-\u03baB pathways. Oncogene. 2020;39(2):428\u201342.","journal-title":"Oncogene"},{"issue":"4","key":"2888_CR46","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1016\/j.cell.2020.07.009","volume":"182","author":"A Hoshino","year":"2020","unstructured":"Hoshino A, Kim HS, Bojmar L, Gyan KE, Cioffi M, Hernandez J, Zambirinis CP, Rodrigues G, Molina H, Heissel S, et al. Extracellular vesicle and particle biomarkers define multiple human cancers. Cell. 2020;182(4):1044\u2013e10611018.","journal-title":"Cell"},{"key":"2888_CR47","doi-asserted-by":"publisher","first-page":"32945","DOI":"10.3402\/jev.v5.32945","volume":"5","author":"C Gardiner","year":"2016","unstructured":"Gardiner C, Di Vizio D, Sahoo S, Th\u00e9ry C, Witwer KW, Wauben M, Hill AF. Techniques used for the isolation and characterization of extracellular vesicles: results of a worldwide survey. J Extracell Vesicles. 2016;5:32945.","journal-title":"J Extracell Vesicles"},{"issue":"4","key":"2888_CR48","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1016\/j.ymthe.2020.02.003","volume":"28","author":"W Yang","year":"2020","unstructured":"Yang W, Zhang J, Xu B, He Y, Liu W, Li J, Zhang S, Lin X, Su D, Wu T, et al. HucMSC-Derived exosomes mitigate the age-related retardation of fertility in female mice. Mol Therapy: J Am Soc Gene Therapy. 2020;28(4):1200\u201313.","journal-title":"Mol Therapy: J Am Soc Gene Therapy"},{"key":"2888_CR49","doi-asserted-by":"crossref","unstructured":"Vuji\u0107 T, Schvartz D, Iliuk A, Sanchez JC. Ubiquinone metabolism and transcription HIF-1 targets pathway are toxicity signature pathways Present in Extracellular vesicles of paraquat-exposed human brain microvascular endothelial cells. Int J Mol Sci 2021, 22(10): 1-12.","DOI":"10.3390\/ijms22105065"},{"issue":"1","key":"2888_CR50","doi-asserted-by":"publisher","first-page":"5395","DOI":"10.1038\/s41467-018-07810-w","volume":"9","author":"Z Zeng","year":"2018","unstructured":"Zeng Z, Li Y, Pan Y, Lan X, Song F, Sun J, Zhou K, Liu X, Ren X, Wang F, et al. Cancer-derived exosomal mir-25-3p promotes pre-metastatic niche formation by inducing vascular permeability and angiogenesis. Nat Commun. 2018;9(1):5395.","journal-title":"Nat Commun"},{"issue":"1","key":"2888_CR51","doi-asserted-by":"publisher","first-page":"17","DOI":"10.7150\/thno.36930","volume":"10","author":"SJ Zhao","year":"2020","unstructured":"Zhao SJ, Kong FQ, Jie J, Li Q, Liu H, Xu AD, Yang YQ, Jiang B, Wang DD, Zhou ZQ, et al. Macrophage MSR1 promotes BMSC osteogenic differentiation and M2-like polarization by activating PI3K\/AKT\/GSK3\u03b2\/\u03b2-catenin pathway. Theranostics. 2020;10(1):17\u201335.","journal-title":"Theranostics"},{"issue":"7","key":"2888_CR52","doi-asserted-by":"publisher","first-page":"2004","DOI":"10.1053\/j.gastro.2022.02.017","volume":"162","author":"X Shi","year":"2022","unstructured":"Shi X, Yang J, Liu M, Zhang Y, Zhou Z, Luo W, Fung KM, Xu C, Bronze MS, Houchen CW, et al. Circular RNA ANAPC7 inhibits Tumor Growth and muscle wasting via PHLPP2-AKT-TGF-\u03b2 Signaling Axis in Pancreatic Cancer. Gastroenterology. 2022;162(7):2004\u201317. e2002.","journal-title":"Gastroenterology"},{"issue":"3","key":"2888_CR53","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.ccell.2017.02.009","volume":"31","author":"DF Quail","year":"2017","unstructured":"Quail DF, Joyce JA. The Microenvironmental Landscape of Brain tumors. Cancer Cell. 2017;31(3):326\u201341.","journal-title":"Cancer Cell"},{"issue":"6","key":"2888_CR54","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1016\/j.ccell.2021.05.002","volume":"39","author":"T Hara","year":"2021","unstructured":"Hara T, Chanoch-Myers R, Mathewson ND, Myskiw C, Atta L, Bussema L, Eichhorn SW, Greenwald AC, Kinker GS, Rodman C, et al. Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma. Cancer Cell. 2021;39(6):779\u2013e792711.","journal-title":"Cancer Cell"},{"issue":"10","key":"2888_CR55","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1016\/j.ccell.2022.08.014","volume":"40","author":"A Chryplewicz","year":"2022","unstructured":"Chryplewicz A, Scotton J, Tichet M, Zomer A, Shchors K, Joyce JA, Homicsko K, Hanahan D. Cancer cell autophagy, reprogrammed macrophages, and remodeled vasculature in glioblastoma triggers tumor immunity. Cancer Cell. 2022;40(10):1111\u2013e11271119.","journal-title":"Cancer Cell"},{"issue":"6","key":"2888_CR56","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1038\/s41590-022-01215-0","volume":"23","author":"AT Yeo","year":"2022","unstructured":"Yeo AT, Rawal S, Delcuze B, Christofides A, Atayde A, Strauss L, Balaj L, Rogers VA, Uhlmann EJ, Varma H, et al. Single-cell RNA sequencing reveals evolution of immune landscape during glioblastoma progression. Nat Immunol. 2022;23(6):971\u201384.","journal-title":"Nat Immunol"},{"issue":"10","key":"2888_CR57","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1038\/ni.2703","volume":"14","author":"TF Gajewski","year":"2013","unstructured":"Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol. 2013;14(10):1014\u201322.","journal-title":"Nat Immunol"},{"issue":"8","key":"2888_CR58","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1038\/s41590-022-01267-2","volume":"23","author":"A Christofides","year":"2022","unstructured":"Christofides A, Strauss L, Yeo A, Cao C, Charest A, Boussiotis VA. The complex role of tumor-infiltrating macrophages. Nat Immunol. 2022;23(8):1148\u201356.","journal-title":"Nat Immunol"},{"issue":"5","key":"2888_CR59","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1016\/j.ccell.2016.09.011","volume":"30","author":"Y Liu","year":"2016","unstructured":"Liu Y, Cao X. Characteristics and significance of the pre-metastatic niche. Cancer Cell. 2016;30(5):668\u201381.","journal-title":"Cancer Cell"},{"issue":"1","key":"2888_CR60","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1186\/s12943-020-01276-5","volume":"19","author":"X Xu","year":"2020","unstructured":"Xu X, Zhang M, Xu F, Jiang S. Wnt signaling in breast cancer: biological mechanisms, challenges and opportunities. Mol Cancer. 2020;19(1):165.","journal-title":"Mol Cancer"},{"issue":"4","key":"2888_CR61","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1016\/j.ccell.2022.02.013","volume":"40","author":"Y Liu","year":"2022","unstructured":"Liu Y, Zhang Q, Xing B, Luo N, Gao R, Yu K, Hu X, Bu Z, Peng J, Ren X, et al. Immune phenotypic linkage between colorectal cancer and liver metastasis. Cancer Cell. 2022;40(4):424\u2013e437425.","journal-title":"Cancer Cell"},{"issue":"1","key":"2888_CR62","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1158\/2159-8290.CD-21-0316","volume":"12","author":"Y Wu","year":"2022","unstructured":"Wu Y, Yang S, Ma J, Chen Z, Song G, Rao D, Cheng Y, Huang S, Liu Y, Jiang S, et al. Spatiotemporal Immune Landscape of Colorectal Cancer Liver Metastasis at single-cell level. Cancer Discov. 2022;12(1):134\u201353.","journal-title":"Cancer Discov"},{"issue":"1","key":"2888_CR63","doi-asserted-by":"publisher","first-page":"3015","DOI":"10.1038\/s41467-020-16827-z","volume":"11","author":"W Tao","year":"2020","unstructured":"Tao W, Chu C, Zhou W, Huang Z, Zhai K, Fang X, Huang Q, Zhang A, Wang X, Yu X, et al. Dual role of WISP1 in maintaining glioma stem cells and tumor-supportive macrophages in glioblastoma. Nat Commun. 2020;11(1):3015.","journal-title":"Nat Commun"},{"issue":"9","key":"2888_CR64","first-page":"1482","volume":"24","author":"Y Zhou","year":"2022","unstructured":"Zhou Y, Meng X, He W, Li X, Zhao R, Dong C, Yuan D, Yang J, Zhang R, Shi G, et al. USF1\/CD90 signaling in maintaining glioblastoma stem cells and tumor-associated macrophages adhesion. Neurooncology. 2022;24(9):1482\u201393.","journal-title":"Neurooncology"},{"issue":"8","key":"2888_CR65","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.1158\/0008-5472.CAN-21-0003","volume":"82","author":"Y Cheng","year":"2022","unstructured":"Cheng Y, Bai F, Ren X, Sun R, Guo X, Liu W, Wang B, Yang Y, Zhang X, Xu Y, et al. Phosphoinositide-binding protein TIPE1 promotes alternative activation of macrophages and Tumor Progression via PIP3\/Akt\/TGF\u03b2 Axis. Cancer Res. 2022;82(8):1603\u201316.","journal-title":"Cancer Res"},{"issue":"18","key":"2888_CR66","doi-asserted-by":"publisher","first-page":"3321","DOI":"10.1158\/0008-5472.CAN-22-0507","volume":"82","author":"D Li","year":"2022","unstructured":"Li D, Zhang Q, Li L, Chen K, Yang J, Dixit D, Gimple RC, Ci S, Lu C, Hu L, et al. beta2-Microglobulin maintains Glioblastoma Stem cells and induces M2-like polarization of Tumor-Associated macrophages. Cancer Res. 2022;82(18):3321\u201334.","journal-title":"Cancer Res"},{"issue":"2","key":"2888_CR67","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1016\/j.bbcan.2019.04.004","volume":"1871","author":"L Zhang","year":"2019","unstructured":"Zhang L, Yu D. Exosomes in cancer development, metastasis, and immunity. Biochim et Biophys acta Reviews cancer. 2019;1871(2):455\u201368.","journal-title":"Biochim et Biophys acta Reviews cancer"},{"issue":"1","key":"2888_CR68","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1186\/s12885-023-11097-6","volume":"23","author":"Z Xue","year":"2023","unstructured":"Xue Z, Wang J, Wang Z, Liu J, Zhao J, Liu X, Zhang Y, Liu G, Zhao Z, Li W, et al. SLC25A32 promotes malignant progression of glioblastoma by activating PI3K-AKT signaling pathway. BMC Cancer. 2023;23(1):589.","journal-title":"BMC Cancer"},{"issue":"3","key":"2888_CR69","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1016\/j.immuni.2018.03.014","volume":"48","author":"C Sun","year":"2018","unstructured":"Sun C, Mezzadra R, Schumacher TN. Regulation and function of the PD-L1 checkpoint. Immunity. 2018;48(3):434\u201352.","journal-title":"Immunity"},{"issue":"1","key":"2888_CR70","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1186\/s12943-020-01258-7","volume":"19","author":"S Zou","year":"2020","unstructured":"Zou S, Tong Q, Liu B, Huang W, Tian Y, Fu X. Targeting STAT3 in Cancer Immunotherapy. Mol Cancer. 2020;19(1):145.","journal-title":"Mol Cancer"},{"key":"2888_CR71","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1146\/annurev-pathol-042020-042741","volume":"16","author":"S Bagchi","year":"2021","unstructured":"Bagchi S, Yuan R, Engleman EG. Immune Checkpoint inhibitors for the treatment of Cancer: clinical impact and mechanisms of response and resistance. Annu Rev Pathol. 2021;16:223\u201349.","journal-title":"Annu Rev Pathol"}],"container-title":["Journal of Nanobiotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12951-024-02888-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12951-024-02888-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12951-024-02888-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T15:06:41Z","timestamp":1729091201000},"score":1,"resource":{"primary":{"URL":"https:\/\/jnanobiotechnology.biomedcentral.com\/articles\/10.1186\/s12951-024-02888-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,16]]},"references-count":71,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["2888"],"URL":"https:\/\/doi.org\/10.1186\/s12951-024-02888-5","relation":{},"ISSN":["1477-3155"],"issn-type":[{"value":"1477-3155","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,16]]},"assertion":[{"value":"28 April 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 September 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 October 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The Scientific Research Ethics Committee of Qilu Hospital, Shandong University examined and approved the study that used human subjects (approval number: KYLL-2017(KS)-090). For their participation in this study, patients and volunteers gave written informed consent. Samples of human glioma tissue were taken during surgery on patients at Qilu Hospital. Due to traumatic brain injury occurrences, non-neoplastic brain tissue samples were collected from patients during surgery. All methods were carried out in accordance with relevant guidelines and regulations. All animal experiments were conducted in compliance with the protocol approved by the Scientific Research Ethics Committee of Qilu Hospital, Shandong University. All animal experiments were performed in accordance with accepted standards of humane animal care.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"628"}}