{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T02:57:27Z","timestamp":1793674647920,"version":"4.5.1"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":38,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"the National Fund for Major Projects of China","award":["2018ZX09301035"],"award-info":[{"award-number":["2018ZX09301035"]}]},{"name":"the Priority Academic Program Development of Jiangsu Higher Education Institutions"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Commun Signal"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Blocking immune checkpoints has become a viable immunotherapy option for cancer. CD47, an anti-phagocytic molecule, engages with SIRP\u03b1 on macrophages to transmit a \u201cdon\u2019t eat me\u201d signal, facilitating immunoevasion. This research examined the molecular pathways influenced by miR-96-5p in pancreatic ductal adenocarcinoma (PDAC) and evaluates its clinical and biological significance. Utilizing bioinformatics, Western blot, luciferase reporter assays and RNA fluorescence in situ hybridization, results revealed that miR-96-5p directly targeted and inversely regulated CD47 expression, indicating patient survival in PDAC. Further investigation into the effects of miR-96-5p on PDAC was conducted through co-culture phagocytosis, antigen presentation, and T cell activation experiments, and mouse PDAC models. The results demonstrated that specifically re-establishing miR-96-5p expression in PDAC cells significantly repressed PDAC tumorigenesis and reprogramed the immunosuppressive microenvironment by diminishing CD47 protein abundance. This modulation encouraged the shift of tumor-associated macrophages (TAMs) into pro-phagocytic M1-like phenotypes via exosomal transfer of miR-96-5p and boosted T cell activation within both peripheral and tumor immune microenvironments. Mechanistically, experiments based on the ovalbumin (OVA) antigen system revealed that the phagocytic function of miR-96-5p enhanced the presentation of tumor antigens to T cells, resulting in more effective activation of antigen-specific T cells, instead of miR-96-5p directly activating T cells. The findings verify that miR-96-5p serves as an effective tumor suppressor, reducing tumor burden by triggering both innate and adaptive anti-tumor immune responses, offering a promising avenue for PDAC immunotherapy improvement.<\/jats:p>","DOI":"10.1186\/s12964-025-02582-5","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T08:07:24Z","timestamp":1764922044000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["miR-96-5p-mediated Inhibition of CD47 contributes to pancreatic tumor regression via activating both innate and adaptive anti-tumor immunity"],"prefix":"10.1186","volume":"24","author":[{"given":"Shoufang","family":"Tong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shushan","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunling","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingxing","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeqing","family":"Leng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengfan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiping","family":"Ou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenfeng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingwei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhua","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"issue":"3","key":"2582_CR1","first-page":"209","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209\u201349.","journal-title":"CA Cancer J Clin"},{"issue":"1","key":"2582_CR2","first-page":"7","volume":"71","author":"RL Siegel","year":"2021","unstructured":"Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer stat 2021 CA cancer J clin. CA Cancer J Clin. 2021;71(1):7\u201333.","journal-title":"CA Cancer J Clin"},{"issue":"10242","key":"2582_CR3","doi-asserted-by":"publisher","first-page":"2008","DOI":"10.1016\/S0140-6736(20)30974-0","volume":"395","author":"JD Mizrahi","year":"2020","unstructured":"Mizrahi JD, Surana R, Valle JW, Shroff RT. Pancreatic cancer. Lancet. 2020;395(10242):2008\u201320.","journal-title":"Lancet"},{"issue":"10039","key":"2582_CR4","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/S0140-6736(16)00141-0","volume":"388","author":"T Kamisawa","year":"2016","unstructured":"Kamisawa T, Wood LD, Itoi T, Takaori K. Pancreat cancer lancet. Lancet. 2016;388(10039):73\u201385.","journal-title":"Lancet"},{"issue":"7","key":"2582_CR5","doi-asserted-by":"publisher","first-page":"2056","DOI":"10.1053\/j.gastro.2018.12.038","volume":"156","author":"VP Balachandran","year":"2019","unstructured":"Balachandran VP, Beatty GL, Dougan SK. Broadening the impact of immunotherapy to pancreatic cancer: challenges and opportunities. Gastroenterology. 2019;156(7):2056\u201372.","journal-title":"Gastroenterology"},{"issue":"5","key":"2582_CR6","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1038\/nm.4082","volume":"22","author":"H Laklai","year":"2016","unstructured":"Laklai H, Miroshnikova YA, Pickup MW, Collisson EA, Kim GE, Barrett AS, et al. Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression. Nat Med. 2016;22(5):497\u2013505.","journal-title":"Nat Med"},{"issue":"50","key":"2582_CR7","doi-asserted-by":"publisher","first-page":"20212","DOI":"10.1073\/pnas.1320318110","volume":"110","author":"C Feig","year":"2013","unstructured":"Feig C, Jones JO, Kraman M, Wells RJ, Deonarine A, Chan DS, et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci U S A. 2013;110(50):20212\u20137.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"2582_CR8","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1186\/s12943-021-01428-1","volume":"20","author":"X Mao","year":"2021","unstructured":"Mao X, Xu J, Wang W, Liang C, Hua J, Liu J, et al. Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives. Mol Cancer. 2021;20(1):131.","journal-title":"Mol Cancer"},{"issue":"2","key":"2582_CR9","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.cell.2009.05.046","volume":"138","author":"S Jaiswal","year":"2009","unstructured":"Jaiswal S, Jamieson CH, Pang WW, Park CY, Chao MP, Majeti R, et al. CD47 is upregulated on Circulating hematopoietic stem cells and leukemia cells to avoid phagocytosis. Cell. 2009;138(2):271\u201385.","journal-title":"Cell"},{"issue":"2","key":"2582_CR10","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.cell.2009.05.045","volume":"138","author":"R Majeti","year":"2009","unstructured":"Majeti R, Chao MP, Alizadeh AA, Pang WW, Jaiswal S, Gibbs KD, et al. CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell. 2009;138(2):286\u201399.","journal-title":"Cell"},{"issue":"17","key":"2582_CR11","doi-asserted-by":"publisher","first-page":"6662","DOI":"10.1073\/pnas.1121623109","volume":"109","author":"SB Willingham","year":"2012","unstructured":"Willingham SB, Volkmer JP, Gentles AJ, Sahoo D, Dalerba P, Mitra SS, et al. The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors. Proc Natl Acad Sci U S A. 2012;109(17):6662\u20137.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"2582_CR12","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/S0962-8924(00)01906-1","volume":"11","author":"EJ Brown","year":"2001","unstructured":"Brown EJ, Frazier WA. Integrin-associated protein (CD47) and its ligands. Trends Cell Biol. 2001;11(3):130\u20135.","journal-title":"Trends Cell Biol"},{"issue":"5","key":"2582_CR13","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1016\/j.immuni.2020.04.011","volume":"52","author":"MEW Logtenberg","year":"2020","unstructured":"Logtenberg MEW, Scheeren FA, Schumacher TN. The CD47-SIRP\u03b1 immune checkpoint. Immunity. 2020;52(5):742\u201352.","journal-title":"Immunity"},{"issue":"27","key":"2582_CR14","doi-asserted-by":"publisher","first-page":"11103","DOI":"10.1073\/pnas.1305569110","volume":"110","author":"D Tseng","year":"2013","unstructured":"Tseng D, Volkmer JP, Willingham SB, Contreras-Trujillo H, Fathman JW, Fernhoff NB, et al. Anti-CD47 antibody-mediated phagocytosis of cancer by macrophages primes an effective antitumor T-cell response. Proc Natl Acad Sci U S A. 2013;110(27):11103\u20138.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"10","key":"2582_CR15","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1038\/nm.3931","volume":"21","author":"X Liu","year":"2015","unstructured":"Liu X, Pu Y, Cron K, Deng L, Kline J, Frazier WA, et al. CD47 blockade triggers T cell-mediated destruction of Immunogenic tumors. Nat Med. 2015;21(10):1209\u201315.","journal-title":"Nat Med"},{"issue":"4","key":"2582_CR16","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1084\/jem.20180870","volume":"216","author":"B Gong","year":"2019","unstructured":"Gong B, Kiyotani K, Sakata S, Nagano S, Kumehara S, Baba S, et al. Secreted PD-L1 variants mediate resistance to PD-L1 blockade therapy in non-small cell lung cancer. J Exp Med. 2019;216(4):982\u20131000.","journal-title":"J Exp Med"},{"issue":"2","key":"2582_CR17","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1056\/NEJMra1703481","volume":"378","author":"MA Postow","year":"2018","unstructured":"Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 2018;378(2):158\u201368.","journal-title":"N Engl J Med"},{"issue":"7308","key":"2582_CR18","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1038\/nature09267","volume":"466","author":"H Guo","year":"2010","unstructured":"Guo H, Ingolia NT, Weissman JS, Bartel DP. Mammalian MicroRNAs predominantly act to decrease target mRNA levels. Nature. 2010;466(7308):835\u201340.","journal-title":"Nature"},{"issue":"7043","key":"2582_CR19","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1038\/nature03702","volume":"435","author":"J Lu","year":"2005","unstructured":"Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435(7043):834\u20138.","journal-title":"Nature"},{"issue":"11","key":"2582_CR20","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1038\/nrc1997","volume":"6","author":"GA Calin","year":"2006","unstructured":"Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857\u201366.","journal-title":"Nat Rev Cancer"},{"issue":"17","key":"2582_CR21","doi-asserted-by":"publisher","first-page":"1768","DOI":"10.1056\/NEJMp058190","volume":"353","author":"CZ Chen","year":"2005","unstructured":"Chen CZ. MicroRNAs as oncogenes and tumor suppressors. N Engl J Med. 2005;353(17):1768\u201371.","journal-title":"N Engl J Med"},{"issue":"1","key":"2582_CR22","doi-asserted-by":"publisher","first-page":"1845","DOI":"10.1038\/s41467-018-03962-x","volume":"9","author":"S Ottaviani","year":"2018","unstructured":"Ottaviani S, Stebbing J, Frampton AE, Zagorac S, Krell J, de Giorgio A, et al. TGF-beta induces miR-100 and miR-125b but blocks let-7a through LIN28B controlling PDAC progression. Nat Commun. 2018;9(1):1845.","journal-title":"Nat Commun"},{"issue":"1","key":"2582_CR23","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s13046-018-0757-8","volume":"37","author":"L Cao","year":"2018","unstructured":"Cao L, Liu Y, Wang D, Huang L, Li F, Liu J, et al. MiR-760 suppresses human colorectal cancer growth by targeting BATF3\/AP-1\/cyclinD1 signaling. J Exp Clin Cancer Res. 2018;37(1):83.","journal-title":"J Exp Clin Cancer Res"},{"key":"2582_CR24","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6241","author":"LM Chen","year":"2014","unstructured":"Chen LM, Gibbons DL, Goswami S, Cortez MA, Ahn YH, Byers LA, et al. Metastasis is regulated via microRNA-200\/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression. Nat Commun. 2014. https:\/\/doi.org\/10.1038\/ncomms6241.","journal-title":"Nat Commun"},{"key":"2582_CR25","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.canlet.2018.05.020","volume":"431","author":"S Hirschberger","year":"2018","unstructured":"Hirschberger S, Hinske LC, Kreth S. MiRNAs: dynamic regulators of immune cell functions in inflammation and cancer. Cancer Lett. 2018;431:11\u201321.","journal-title":"Cancer Lett"},{"issue":"1","key":"2582_CR26","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1158\/0008-5472.CAN-12-0271","volume":"73","author":"PN Plummer","year":"2013","unstructured":"Plummer PN, Freeman R, Taft RJ, Vider J, Sax M, Umer BA, et al. MicroRNAs regulate tumor angiogenesis modulated by endothelial progenitor cells. Cancer Res. 2013;73(1):341\u201352.","journal-title":"Cancer Res"},{"issue":"Database issue","key":"2582_CR27","doi-asserted-by":"publisher","first-page":"D92","DOI":"10.1093\/nar\/gkt1248","volume":"42","author":"JH Li","year":"2014","unstructured":"Li JH, Liu S, Zhou H, Qu LH, Yang JH. StarBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 2014;42(Database issue):D92\u20137.","journal-title":"Nucleic Acids Res"},{"key":"2582_CR28","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.05005","author":"V Agarwal","year":"2015","unstructured":"Agarwal V, Bell GW, Nam JW, Bartel DP. Predicting effective MicroRNA target sites in mammalian mRNAs. Elife. 2015. https:\/\/doi.org\/10.7554\/eLife.05005.","journal-title":"Elife"},{"issue":"W1","key":"2582_CR29","doi-asserted-by":"publisher","first-page":"W169","DOI":"10.1093\/nar\/gkt393","volume":"41","author":"MD Paraskevopoulou","year":"2013","unstructured":"Paraskevopoulou MD, Georgakilas G, Kostoulas N, Vlachos IS, Vergoulis T, Reczko M, et al. DIANA-microT web server v5.0: service integration into MiRNA functional analysis workflows. Nucleic Acids Res. 2013;41(W1):W169\u201373.","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"2582_CR30","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/ng1536","volume":"37","author":"A Krek","year":"2005","unstructured":"Krek A, Gr\u00fcn D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, et al. Combinatorial microRNA target predictions. Nat Genet. 2005;37(5):495\u2013500.","journal-title":"Nat Genet"},{"issue":"W1","key":"2582_CR31","doi-asserted-by":"publisher","first-page":"W98","DOI":"10.1093\/nar\/gkx247","volume":"45","author":"ZF Tang","year":"2017","unstructured":"Tang ZF, Li CW, Kang BX, Gao G, Li C, Zhang ZM. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98\u2013102.","journal-title":"Nucleic Acids Res"},{"issue":"D1","key":"2582_CR32","doi-asserted-by":"publisher","first-page":"D956","DOI":"10.1093\/nar\/gkx1090","volume":"46","author":"SV Vasaikar","year":"2018","unstructured":"Vasaikar SV, Straub P, Wang J, Zhang B. LinkedOmics: analyzing multi-omics data within and across 32 cancer types. Nucleic Acids Res. 2018;46(D1):D956\u201363.","journal-title":"Nucleic Acids Res"},{"issue":"W1","key":"2582_CR33","doi-asserted-by":"publisher","first-page":"W460","DOI":"10.1093\/nar\/gkv403","volume":"43","author":"IS Vlachos","year":"2015","unstructured":"Vlachos IS, Zagganas K, Paraskevopoulou MD, Georgakilas G, Karagkouni D, Vergoulis T, et al. DIANA-miRPath v3.0: Deciphering MicroRNA function with experimental support. Nucleic Acids Res. 2015;43(W1):W460\u20136.","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"2582_CR34","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1089\/hgtb.2016.089","volume":"28","author":"M Chen","year":"2017","unstructured":"Chen M, Maeng K, Nawab A, Francois RA, Bray JK, Reinhard MK, et al. Efficient gene delivery and expression in pancreas and pancreatic tumors by Capsid-Optimized AAV8 vectors. Hum Gene Ther Methods. 2017;28(1):49\u201359.","journal-title":"Hum Gene Ther Methods"},{"key":"2582_CR35","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2023.216205","volume":"564","author":"J Lu","year":"2023","unstructured":"Lu J, Li J, Lin Z, Li H, Lou L, Ding W, et al. Reprogramming of TAMs via the STAT3\/CD47-SIRP\u03b1 axis promotes acquired resistance to EGFR-TKIs in lung cancer. Cancer Lett. 2023;564:216205.","journal-title":"Cancer Lett"},{"issue":"1","key":"2582_CR36","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1532","volume":"14","author":"YG Shen","year":"2024","unstructured":"Shen YG, Ji MM, Yi HM, Shen R, Fu D, Cheng S, et al. CD47 overexpression is related to tumour-associated macrophage infiltration and diffuse large B-cell lymphoma progression. Clin Transl Med. 2024;14(1):e1532.","journal-title":"Clin Transl Med"},{"issue":"3","key":"2582_CR37","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1038\/s41596-019-0249-0","volume":"15","author":"DKY Zhang","year":"2020","unstructured":"Zhang DKY, Cheung AS, Mooney DJ. Activation and expansion of human T cells using artificial antigen-presenting cell scaffolds. Nat Protoc. 2020;15(3):773\u201398.","journal-title":"Nat Protoc"},{"issue":"1","key":"2582_CR38","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1186\/s13045-019-0822-6","volume":"12","author":"Y Pan","year":"2019","unstructured":"Pan Y, Lu F, Fei Q, Yu X, Xiong P, Yu X, et al. Single-cell RNA sequencing reveals compartmental remodeling of tumor-infiltrating immune cells induced by anti-CD47 targeting in pancreatic cancer. J Hematol Oncol. 2019;12(1):124.","journal-title":"J Hematol Oncol"},{"key":"2582_CR39","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106264","volume":"181","author":"A Alausa","year":"2022","unstructured":"Alausa A, Lawal KA, Babatunde OA, Obiwulu ENO, Oladokun OC, Fadahunsi OS, et al. Overcoming immunotherapeutic resistance in PDAC: SIRP\u03b1-CD47 blockade. Pharmacol Res. 2022;181:106264.","journal-title":"Pharmacol Res"},{"issue":"5","key":"2582_CR40","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1038\/nri2761","volume":"10","author":"AC Chan","year":"2010","unstructured":"Chan AC, Carter PJ. Therapeutic antibodies for autoimmunity and inflammation. Nat Rev Immunol. 2010;10(5):301\u201316.","journal-title":"Nat Rev Immunol"},{"issue":"31","key":"2582_CR41","doi-asserted-by":"publisher","first-page":"4893","DOI":"10.1200\/JCO.22.02604","volume":"41","author":"NG Daver","year":"2023","unstructured":"Daver NG, Vyas P, Kambhampati S, Al Malki MM, Larson RA, Asch AS, et al. Tolerability and efficacy of the anticluster of differentiation 47 antibody Magrolimab combined with Azacitidine in patients with previously untreated AML: phase Ib results. J Clin Oncol. 2023;41(31):4893\u2013904.","journal-title":"J Clin Oncol"},{"key":"2582_CR42","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.807895","author":"ZJ Zhang","year":"2022","unstructured":"Zhang ZJ, Huang QC, Yu LCY, Zhu DJ, Li Y, Xue ZY, et al. The role of MiRNA in tumor immune escape and MiRNA-based therapeutic strategies. Front Immunol. 2022. https:\/\/doi.org\/10.3389\/fimmu.2021.807895.","journal-title":"Front Immunol"},{"issue":"1","key":"2582_CR43","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s12943-018-0768-2","volume":"17","author":"W Huang","year":"2018","unstructured":"Huang W, Wang WT, Fang K, Chen ZH, Sun YM, Han C, et al. MIR-708 promotes phagocytosis to eradicate T-ALL cells by targeting CD47. Mol Cancer. 2018;17(1):12.","journal-title":"Mol Cancer"},{"key":"2582_CR44","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2019-000253","author":"Q Xi","year":"2020","unstructured":"Xi Q, Zhang J, Yang G, Zhang L, Chen Y, Wang C, et al. Restoration of miR-340 controls pancreatic cancer cell CD47 expression to promote macrophage phagocytosis and enhance antitumor immunity. J Immunother Cancer. 2020. https:\/\/doi.org\/10.1136\/jitc-2019-000253.","journal-title":"J Immunother Cancer"},{"issue":"7","key":"2582_CR45","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.1016\/j.cell.2007.04.040","volume":"129","author":"P Landgraf","year":"2007","unstructured":"Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A, et al. A mammalian MicroRNA expression atlas based on small RNA library sequencing. Cell. 2007;129(7):1401\u201314.","journal-title":"Cell"},{"issue":"1","key":"2582_CR46","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1186\/s12943-022-01611-y","volume":"21","author":"M Wu","year":"2022","unstructured":"Wu M, Qiu Q, Zhou Q, Li J, Yang J, Zheng C, et al. circFBXO7\/miR-96-5p\/MTSS1 axis is an important regulator in the Wnt signaling pathway in ovarian cancer. Mol Cancer. 2022;21(1):137.","journal-title":"Mol Cancer"},{"issue":"1","key":"2582_CR47","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1186\/s12951-025-03306-0","volume":"23","author":"Q Xiao","year":"2025","unstructured":"Xiao Q, Tan M, Yan G, Peng L. Revolutionizing lung cancer treatment: harnessing exosomes as early diagnostic biomarkers, therapeutics and nano-delivery platforms. J Nanobiotechnol. 2025;23(1):232.","journal-title":"J Nanobiotechnol"},{"issue":"8","key":"2582_CR48","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":"8","key":"2582_CR49","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1038\/s41551-018-0236-8","volume":"2","author":"CB Rodell","year":"2018","unstructured":"Rodell CB, Arlauckas SP, Cuccarese MF, Garris CS, Li R, Ahmed MS, et al. TLR7\/8-agonist-loaded nanoparticles promote the polarization of tumour-associated macrophages to enhance cancer immunotherapy. Nat Biomed Eng. 2018;2(8):578\u201388.","journal-title":"Nat Biomed Eng"},{"issue":"2","key":"2582_CR50","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1038\/s41577-022-00737-w","volume":"23","author":"S Goswami","year":"2023","unstructured":"Goswami S, Anandhan S, Raychaudhuri D, Sharma P. Myeloid cell-targeted therapies for solid tumours. Nat Rev Immunol. 2023;23(2):106\u201320.","journal-title":"Nat Rev Immunol"},{"issue":"4","key":"2582_CR51","doi-asserted-by":"publisher","first-page":"e0153550","DOI":"10.1371\/journal.pone.0153550","volume":"11","author":"M Zhang","year":"2016","unstructured":"Zhang M, Hutter G, Kahn SA, Azad TD, Gholamin S, Xu CY, et al. Anti-CD47 treatment stimulates phagocytosis of glioblastoma by M1 and M2 polarized macrophages and promotes M1 polarized macrophages in vivo. PLoS One. 2016;11(4):e0153550.","journal-title":"PLoS One"},{"issue":"8","key":"2582_CR52","doi-asserted-by":"publisher","first-page":"1610","DOI":"10.1016\/j.cell.2023.03.010","volume":"186","author":"R Kalluri","year":"2023","unstructured":"Kalluri R, McAndrews KM. The role of extracellular vesicles in cancer. Cell. 2023;186(8):1610\u201326.","journal-title":"Cell"},{"issue":"1","key":"2582_CR53","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20527-z","volume":"12","author":"B Li","year":"2021","unstructured":"Li B, Zhu L, Lu C, Wang C. circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity. Nat Commun. 2021;12(1):295.","journal-title":"Nat Commun"},{"issue":"10","key":"2582_CR54","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1038\/s41568-019-0183-z","volume":"19","author":"M Feng","year":"2019","unstructured":"Feng M, Jiang W, Kim BYS, Zhang CC, Fu YX, Weissman IL. Phagocytosis checkpoints as new targets for cancer immunotherapy. Nat Rev Cancer. 2019;19(10):568\u201386.","journal-title":"Nat Rev Cancer"},{"issue":"15","key":"2582_CR55","doi-asserted-by":"publisher","first-page":"5214","DOI":"10.1158\/0008-5472.CAN-10-4645","volume":"71","author":"AF Ibrahim","year":"2011","unstructured":"Ibrahim AF, Weirauch U, Thomas M, Gr\u00fcnweller A, Hartmann RK, Aigner A. MicroRNA replacement therapy for miR-145 and miR-33a is efficacious in a model of colon carcinoma. Cancer Res. 2011;71(15):5214\u201324.","journal-title":"Cancer Res"},{"issue":"11","key":"2582_CR56","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1038\/s41416-020-0802-1","volume":"122","author":"DS Hong","year":"2020","unstructured":"Hong DS, Kang YK, Borad M, Sachdev J, Ejadi S, Lim HY, et al. Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours. Br J Cancer. 2020;122(11):1630\u20137.","journal-title":"Br J Cancer"},{"issue":"4","key":"2582_CR57","doi-asserted-by":"publisher","first-page":"1714","DOI":"10.1021\/acs.molpharmaceut.9b00065","volume":"16","author":"X Zang","year":"2019","unstructured":"Zang X, Zhang X, Zhao X, Hu H, Qiao M, Deng Y, et al. Targeted delivery of MiRNA 155 to tumor associated macrophages for tumor immunotherapy. Mol Pharm. 2019;16(4):1714\u201322.","journal-title":"Mol Pharm"},{"issue":"4","key":"2582_CR58","doi-asserted-by":"publisher","first-page":"e0190321","DOI":"10.1128\/jvi.01903-21","volume":"96","author":"M Panigrahi","year":"2022","unstructured":"Panigrahi M, Thibault PA, Wilson JA. MicroRNA 122 affects both the initiation and the maintenance of hepatitis C virus infections. J Virol. 2022;96(4):e0190321.","journal-title":"J Virol"},{"issue":"6","key":"2582_CR59","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1016\/j.tig.2022.02.006","volume":"38","author":"C Diener","year":"2022","unstructured":"Diener C, Keller A, Meese E. Emerging concepts of MiRNA therapeutics: from cells to clinic. Trends Genet. 2022;38(6):613\u201326.","journal-title":"Trends Genet"},{"issue":"13","key":"2582_CR60","first-page":"7027","volume":"48","author":"H Liang","year":"2020","unstructured":"Liang H, Jiao Z, Rong W, Qu S, Liao Z, Sun X, et al. 3\u2019-Terminal 2\u2019-O-methylation of lung cancer miR-21-5p enhances its stability and association with argonaute 2. Nucleic Acids Res. 2020;48(13):7027\u201340.","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"2582_CR61","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s13045-023-01468-8","volume":"16","author":"P Tassone","year":"2023","unstructured":"Tassone P, Di Martino MT, Arbitrio M, Fiorillo L, Staropoli N, Ciliberto D, et al. Safety and activity of the first-in-class locked nucleic acid (LNA) miR-221 selective inhibitor in refractory advanced cancer patients: a first-in-human, phase 1, open-label, dose-escalation study. J Hematol Oncol. 2023;16(1):68.","journal-title":"J Hematol Oncol"}],"container-title":["Cell Communication and Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-025-02582-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12964-025-02582-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-025-02582-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T15:02:48Z","timestamp":1781622168000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12964-025-02582-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,5]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2582"],"URL":"https:\/\/doi.org\/10.1186\/s12964-025-02582-5","relation":{},"ISSN":["1478-811X"],"issn-type":[{"value":"1478-811X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,5]]},"assertion":[{"value":"11 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 December 2025","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 authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"16"}}