{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T01:12:00Z","timestamp":1775610720904,"version":"3.50.1"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,8,12]],"date-time":"2019-08-12T00:00:00Z","timestamp":1565568000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,8,12]],"date-time":"2019-08-12T00:00:00Z","timestamp":1565568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-13-PRCRP-IA"],"award-info":[{"award-number":["W81XWH-13-PRCRP-IA"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Malignant mesothelioma (MM) is an asbestos-induced cancer arising on the mesothelial surface of organ cavities. MM is essentially incurable without a means of early diagnosis and no successful standard of care. These facts indicate a deep chasm of knowledge that needs to be filled. Our group recently delved into MM tumor biology from the perspective of exosome-contained microRNAs (miRNAs). We discovered that the most abundant miRNAs in MM cancer exosomes were tumor suppressors, particularly miR-16-5p. This observation lead us to hypothesize that MM cells preferentially secreted tumor-suppressor miRNAs via exosomes. Through separate avenues of potential therapeutic advance, we embarked on an innovative strategy to kill MM tumor cells. We employed small molecule inhibitors to block exosome secretion, thereby reducing miR-16-5p exosome loss and replenishing cellular miR-16-5p leading to reduced tumorigenic capacity and miR-16-5p target oncoproteins CCND1 and BCL2. Additionally, we force-fed MM tumor exosomes back to MM tumor cells, which led to cell death, and a reduction in the same oncoproteins. We recapitulated these results with direct transfection of miR-16-5p, confirmed that this is a cancer-cell specific effect, and elucidated a part of the miR-16-5p mechanism of exosome loading.<\/jats:p>","DOI":"10.1038\/s41598-019-48133-0","type":"journal-article","created":{"date-parts":[[2019,8,12]],"date-time":"2019-08-12T10:03:15Z","timestamp":1565604195000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Exosomal miR-16-5p as a target for malignant mesothelioma"],"prefix":"10.1038","volume":"9","author":[{"given":"Phillip B.","family":"Munson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth M.","family":"Hall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas H.","family":"Farina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harvey I.","family":"Pass","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arti","family":"Shukla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,8,12]]},"reference":[{"key":"48133_CR1","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1016\/j.ajpath.2012.12.028","volume":"182","author":"BT Mossman","year":"2013","unstructured":"Mossman, B. T. et al. New insights into understanding the mechanisms, pathogenesis, and management of malignant mesotheliomas. The American journal of pathology 182, 1065\u20131077, https:\/\/doi.org\/10.1016\/j.ajpath.2012.12.028 (2013).","journal-title":"The American journal of pathology"},{"key":"48133_CR2","doi-asserted-by":"publisher","first-page":"91","DOI":"10.3389\/fonc.2018.00091","volume":"8","author":"M Rossini","year":"2018","unstructured":"Rossini, M. et al. New Perspectives on Diagnosis and Therapy of Malignant Pleural Mesothelioma. Frontiers in oncology 8, 91, https:\/\/doi.org\/10.3389\/fonc.2018.00091 (2018).","journal-title":"Frontiers in oncology"},{"key":"48133_CR3","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1038\/nrc.2017.42","volume":"17","author":"TA Yap","year":"2017","unstructured":"Yap, T. A., Aerts, J. G., Popat, S. & Fennell, D. A. Novel insights into mesothelioma biology and implications for therapy. Nature reviews. Cancer 17, 475\u2013488, https:\/\/doi.org\/10.1038\/nrc.2017.42 (2017).","journal-title":"Nature reviews. Cancer"},{"key":"48133_CR4","doi-asserted-by":"publisher","first-page":"310","DOI":"10.3390\/medicines2040310","volume":"2","author":"P Munson","year":"2015","unstructured":"Munson, P. & Shukla, A. Exosomes: Potential in Cancer Diagnosis and Therapy. Medicines 2, 310\u2013327, https:\/\/doi.org\/10.3390\/medicines2040310 (2015).","journal-title":"Medicines"},{"issue":"8","key":"48133_CR5","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1111\/cas.12715","volume":"106","author":"Dan-dan Yu","year":"2015","unstructured":"Yu, D. D. et al. Exosomes in Development, Metastasis and Drug Resistance of Breast Cancer. Cancer science, https:\/\/doi.org\/10.1111\/cas.12715 (2015).","journal-title":"Cancer Science"},{"key":"48133_CR6","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1007\/s00018-014-1764-3","volume":"72","author":"LT Brinton","year":"2015","unstructured":"Brinton, L. T., Sloane, H. S., Kester, M. & Kelly, K. A. Formation and role of exosomes in cancer. Cellular and molecular life sciences: CMLS 72, 659\u2013671, https:\/\/doi.org\/10.1007\/s00018-014-1764-3 (2015).","journal-title":"Cellular and molecular life sciences: CMLS"},{"key":"48133_CR7","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1165\/rcmb.2003-0238OC","volume":"31","author":"MP Bard","year":"2004","unstructured":"Bard, M. P. et al. Proteomic analysis of exosomes isolated from human malignant pleural effusions. American journal of respiratory cell and molecular biology 31, 114\u2013121, https:\/\/doi.org\/10.1165\/rcmb.2003-0238OC (2004).","journal-title":"American journal of respiratory cell and molecular biology"},{"key":"48133_CR8","doi-asserted-by":"publisher","first-page":"1807","DOI":"10.1016\/s0002-9440(10)63739-x","volume":"164","author":"JP Hegmans","year":"2004","unstructured":"Hegmans, J. P. et al. Proteomic analysis of exosomes secreted by human mesothelioma cells. The American journal of pathology 164, 1807\u20131815, https:\/\/doi.org\/10.1016\/s0002-9440(10)63739-x (2004).","journal-title":"The American journal of pathology"},{"issue":"1","key":"48133_CR9","doi-asserted-by":"publisher","first-page":"22492","DOI":"10.3402\/jev.v2i0.22492","volume":"2","author":"Niken M. Mahaweni","year":"2013","unstructured":"Mahaweni, N. M., Kaijen-Lambers, M. E., Dekkers, J., Aerts, J. G. & Hegmans, J. P. Tumour-derived exosomes as antigen delivery carriers in dendritic cell-based immunotherapy for malignant mesothelioma. Journal of extracellular vesicles 2, https:\/\/doi.org\/10.3402\/jev.v2i0.22492 (2013).","journal-title":"Journal of Extracellular Vesicles"},{"key":"48133_CR10","doi-asserted-by":"publisher","DOI":"10.1038\/srep32643","volume":"6","author":"DW Greening","year":"2016","unstructured":"Greening, D. W. et al. Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo. Scientific reports 6, 32643, https:\/\/doi.org\/10.1038\/srep32643 (2016).","journal-title":"Scientific reports"},{"key":"48133_CR11","doi-asserted-by":"publisher","first-page":"45","DOI":"10.4331\/wjbc.v8.i1.45","volume":"8","author":"S Oliveto","year":"2017","unstructured":"Oliveto, S., Mancino, M., Manfrini, N. & Biffo, S. Role of microRNAs in translation regulation and cancer. World journal of biological chemistry 8, 45\u201356, https:\/\/doi.org\/10.4331\/wjbc.v8.i1.45 (2017).","journal-title":"World journal of biological chemistry"},{"key":"48133_CR12","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.3978\/j.issn.2072-1439.2015.04.56","volume":"7","author":"G Reid","year":"2015","unstructured":"Reid, G. MicroRNAs in mesothelioma: from tumour suppressors and biomarkers to therapeutic targets. Journal of thoracic disease 7, 1031\u20131040, https:\/\/doi.org\/10.3978\/j.issn.2072-1439.2015.04.56 (2015).","journal-title":"Journal of thoracic disease"},{"key":"48133_CR13","doi-asserted-by":"publisher","first-page":"5741","DOI":"10.1158\/0008-5472.CAN-18-0655","volume":"78","author":"S Oliveto","year":"2018","unstructured":"Oliveto, S. et al. A Polysome-Based microRNA Screen Identifies miR-24-3p as a Novel Promigratory miRNA in Mesothelioma. Cancer research 78, 5741\u20135753, https:\/\/doi.org\/10.1158\/0008-5472.CAN-18-0655 (2018).","journal-title":"Cancer research"},{"key":"48133_CR14","doi-asserted-by":"publisher","first-page":"58606","DOI":"10.18632\/oncotarget.9686","volume":"7","author":"L Micolucci","year":"2016","unstructured":"Micolucci, L., Akhtar, M. M., Olivieri, F., Rippo, M. R. & Procopio, A. D. Diagnostic value of microRNAs in asbestos exposure and malignant mesothelioma: systematic review and qualitative meta-analysis. Oncotarget 7, 58606\u201358637, https:\/\/doi.org\/10.18632\/oncotarget.9686 (2016).","journal-title":"Oncotarget"},{"key":"48133_CR15","doi-asserted-by":"publisher","first-page":"e0176680","DOI":"10.1371\/journal.pone.0176680","volume":"12","author":"T Cavalleri","year":"2017","unstructured":"Cavalleri, T. et al. Plasmatic extracellular vesicle microRNAs in malignant pleural mesothelioma and asbestos-exposed subjects suggest a 2-miRNA signature as potential biomarker of disease. PLoS ONE 12, e0176680, https:\/\/doi.org\/10.1371\/journal.pone.0176680 (2017).","journal-title":"PLoS ONE"},{"key":"48133_CR16","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.26863","author":"P Munson","year":"2018","unstructured":"Munson, P., Lam, Y. W., MacPherson, M., Beuschel, S. & Shukla, A. Mouse serum exosomal proteomic signature in response to asbestos exposure. Journal of cellular biochemistry. https:\/\/doi.org\/10.1002\/jcb.26863 (2018).","journal-title":"Journal of cellular biochemistry"},{"issue":"8","key":"48133_CR17","doi-asserted-by":"publisher","first-page":"4328","DOI":"10.1096\/fj.201701291RR","volume":"32","author":"Phillip Munson","year":"2018","unstructured":"Munson, P., Lam, Y. W., Dragon, J., MacPherson, M. & Shukla, A. Exosomes from asbestos-exposed cells modulate gene expression in mesothelial cells. FASEB journal: official publication of the Federation of American Societies for Experimental Biology, fj201701291RR, https:\/\/doi.org\/10.1096\/fj.201701291RR (2018).","journal-title":"The FASEB Journal"},{"key":"48133_CR18","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1158\/1541-7786.mcr-11-0337","volume":"10","author":"LE Young","year":"2012","unstructured":"Young, L. E., Moore, A. E., Sokol, L., Meisner-Kober, N. & Dixon, D. A. The mRNA stability factor HuR inhibits microRNA-16 targeting of COX-2. Molecular cancer research: MCR 10, 167\u2013180, https:\/\/doi.org\/10.1158\/1541-7786.mcr-11-0337 (2012).","journal-title":"Molecular cancer research: MCR"},{"key":"48133_CR19","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1002\/jcb.22762","volume":"111","author":"F Xu","year":"2010","unstructured":"Xu, F. et al. Loss of Repression of HuR Translation by miR-16 May Be Responsible for the Elevation of HuR in Human Breast Carcinoma. Journal of cellular biochemistry 111, 727\u2013734, https:\/\/doi.org\/10.1002\/jcb.22762 (2010).","journal-title":"Journal of cellular biochemistry"},{"key":"48133_CR20","doi-asserted-by":"publisher","first-page":"42","DOI":"10.3816\/CLC.2009.n.006","volume":"10","author":"G Rabinowits","year":"2009","unstructured":"Rabinowits, G., Gercel-Taylor, C., Day, J. M., Taylor, D. D. & Kloecker, G. H. Exosomal microRNA: a diagnostic marker for lung cancer. Clinical lung cancer 10, 42\u201346, https:\/\/doi.org\/10.3816\/CLC.2009.n.006 (2009).","journal-title":"Clinical lung cancer"},{"key":"48133_CR21","doi-asserted-by":"publisher","first-page":"14888","DOI":"10.1073\/pnas.1408301111","volume":"111","author":"JR Chevillet","year":"2014","unstructured":"Chevillet, J. R. et al. Quantitative and stoichiometric analysis of the microRNA content of exosomes. Proceedings of the National Academy of Sciences of the United States of America 111, 14888\u201314893, https:\/\/doi.org\/10.1073\/pnas.1408301111 (2014).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"48133_CR22","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1016\/j.ccell.2014.09.005","volume":"26","author":"SA Melo","year":"2014","unstructured":"Melo, S. A. et al. Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer cell 26, 707\u2013721, https:\/\/doi.org\/10.1016\/j.ccell.2014.09.005 (2014).","journal-title":"Cancer cell"},{"key":"48133_CR23","doi-asserted-by":"publisher","first-page":"13944","DOI":"10.1073\/pnas.0506654102","volume":"102","author":"A Cimmino","year":"2005","unstructured":"Cimmino, A. et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proceedings of the National Academy of Sciences of the United States of America 102, 13944\u201313949, https:\/\/doi.org\/10.1073\/pnas.0506654102 (2005).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"48133_CR24","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.26355\/eurrev_201803_14464","volume":"22","author":"DW Wang","year":"2018","unstructured":"Wang, D. W., Wang, Y. Q. & Shu, H. S. MiR-16 inhibits pituitary adenoma cell proliferation via the suppression of ERK\/MAPK signal pathway. European review for medical and pharmacological sciences 22, 1241\u20131248, https:\/\/doi.org\/10.26355\/eurrev_201803_14464 (2018).","journal-title":"European review for medical and pharmacological sciences"},{"key":"48133_CR25","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1016\/j.jtho.2017.05.024","volume":"12","author":"SC Kao","year":"2017","unstructured":"Kao, S. C. et al. Tumor Suppressor microRNAs Contribute to the Regulation of PD-L1 Expression in Malignant Pleural Mesothelioma. Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 12, 1421\u20131433, https:\/\/doi.org\/10.1016\/j.jtho.2017.05.024 (2017).","journal-title":"Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer"},{"key":"48133_CR26","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-02694-0","volume":"7","author":"C De Santi","year":"2017","unstructured":"De Santi, C. et al. Deregulation of miRNAs in malignant pleural mesothelioma is associated with prognosis and suggests an alteration of cell metabolism. Scientific reports 7, 3140, https:\/\/doi.org\/10.1038\/s41598-017-02694-0 (2017).","journal-title":"Scientific reports"},{"key":"48133_CR27","doi-asserted-by":"publisher","first-page":"3128","DOI":"10.1093\/annonc\/mdt412","volume":"24","author":"G Reid","year":"2013","unstructured":"Reid, G. et al. Restoring expression of miR-16: a novel approach to therapy for malignant pleural mesothelioma. Annals of oncology: official journal of the European Society for Medical Oncology 24, 3128\u20133135, https:\/\/doi.org\/10.1093\/annonc\/mdt412 (2013).","journal-title":"Annals of oncology: official journal of the European Society for Medical Oncology"},{"key":"48133_CR28","doi-asserted-by":"crossref","unstructured":"Viteri, S. & Rosell, R. An innovative mesothelioma treatment based on miR-16 mimic loaded EGFR targeted minicells (TargomiRs). Translational Lung Cancer Research, S1\u2013S4 (2017).","DOI":"10.21037\/tlcr.2017.12.01"},{"key":"48133_CR29","doi-asserted-by":"publisher","first-page":"7194","DOI":"10.1158\/0008-5472.can-16-0714","volume":"76","author":"P Kanlikilicer","year":"2016","unstructured":"Kanlikilicer, P. et al. Ubiquitous Release of Exosomal Tumor Suppressor miR-6126 from Ovarian Cancer Cells. Cancer research 76, 7194\u20137207, https:\/\/doi.org\/10.1158\/0008-5472.can-16-0714 (2016).","journal-title":"Cancer research"},{"key":"48133_CR30","doi-asserted-by":"publisher","first-page":"2865","DOI":"10.1007\/s00018-014-1584-5","volume":"71","author":"A Truini","year":"2014","unstructured":"Truini, A. et al. Role of microRNAs in malignant mesothelioma. Cellular and Molecular Life Sciences 71, 2865\u20132878, https:\/\/doi.org\/10.1007\/s00018-014-1584-5 (2014).","journal-title":"Cellular and Molecular Life Sciences"},{"key":"48133_CR31","doi-asserted-by":"publisher","first-page":"78193","DOI":"10.18632\/oncotarget.20409","volume":"8","author":"KA Birnie","year":"2017","unstructured":"Birnie, K. A., Pr\u00eale, C. M., Thompson, P. J., Badrian, B. & Mutsaers, S. E. Targeting microRNA to improve diagnostic and therapeutic approaches for malignant mesothelioma. Oncotarget 8, 78193\u201378207, https:\/\/doi.org\/10.18632\/oncotarget.20409 (2017).","journal-title":"Oncotarget"},{"key":"48133_CR32","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.lungcan.2015.11.002","volume":"90","author":"L Quinn","year":"2015","unstructured":"Quinn, L., Finn, S. P., Cuffe, S., Gray, S. G. & Non-coding, R. N. A. repertoires in malignant pleural mesothelioma. Lung cancer (Amsterdam, Netherlands) 90, 417\u2013426, https:\/\/doi.org\/10.1016\/j.lungcan.2015.11.002 (2015).","journal-title":"Lung cancer (Amsterdam, Netherlands)"},{"key":"48133_CR33","doi-asserted-by":"publisher","first-page":"17442","DOI":"10.1074\/jbc.M110.107821","volume":"285","author":"N Kosaka","year":"2010","unstructured":"Kosaka, N. et al. Secretory Mechanisms and Intercellular Transfer of MicroRNAs in Living Cells. J Biol Chem 285, 17442\u201317452, https:\/\/doi.org\/10.1074\/jbc.M110.107821 (2010).","journal-title":"J Biol Chem"},{"key":"48133_CR34","doi-asserted-by":"publisher","first-page":"2362","DOI":"10.1016\/j.bbadis.2015.08.010","volume":"1852","author":"K Essandoh","year":"2015","unstructured":"Essandoh, K. et al. Blockade of exosome generation with GW4869 dampens the sepsis-induced inflammation and cardiac dysfunction. Biochimica et biophysica acta 1852, 2362\u20132371, https:\/\/doi.org\/10.1016\/j.bbadis.2015.08.010 (2015).","journal-title":"Biochimica et biophysica acta"},{"issue":"5","key":"48133_CR35","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.3390\/ijms18051007","volume":"18","author":"Uchini Kosgodage","year":"2017","unstructured":"Kosgodage, U. S., Trindade, R. P., Thompson, P. R., Inal, J. M. & Lange, S. Chloramidine\/Bisindolylmaleimide-I-Mediated Inhibition of Exosome and Microvesicle Release and Enhanced Efficacy of Cancer Chemotherapy. International journal of molecular sciences 18, https:\/\/doi.org\/10.3390\/ijms18051007 (2017).","journal-title":"International Journal of Molecular Sciences"},{"key":"48133_CR36","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1186\/1479-5876-10-134","volume":"10","author":"AM Marleau","year":"2012","unstructured":"Marleau, A. M., Chen, C.-S., Joyce, J. A. & Tullis, R. H. Exosome removal as a therapeutic adjuvant in cancer. Journal of translational medicine 10, 134\u2013134, https:\/\/doi.org\/10.1186\/1479-5876-10-134 (2012).","journal-title":"Journal of translational medicine"},{"key":"48133_CR37","doi-asserted-by":"publisher","first-page":"1595","DOI":"10.1158\/1535-7163.mct-05-0102","volume":"4","author":"R Safaei","year":"2005","unstructured":"Safaei, R. et al. Abnormal lysosomal trafficking and enhanced exosomal export of cisplatin in drug-resistant human ovarian carcinoma cells. Molecular cancer therapeutics 4, 1595\u20131604, https:\/\/doi.org\/10.1158\/1535-7163.mct-05-0102 (2005).","journal-title":"Molecular cancer therapeutics"},{"key":"48133_CR38","doi-asserted-by":"publisher","first-page":"2912","DOI":"10.1158\/0008-5472.can-07-0520","volume":"67","author":"R Valenti","year":"2007","unstructured":"Valenti, R. et al. Tumor-released microvesicles as vehicles of immunosuppression. Cancer research 67, 2912\u20132915, https:\/\/doi.org\/10.1158\/0008-5472.can-07-0520 (2007).","journal-title":"Cancer research"},{"key":"48133_CR39","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1038\/sj.cdd.4402237","volume":"15","author":"M Iero","year":"2008","unstructured":"Iero, M. et al. Tumour-released exosomes and their implications in cancer immunity. Cell death and differentiation 15, 80\u201388, https:\/\/doi.org\/10.1038\/sj.cdd.4402237 (2008).","journal-title":"Cell death and differentiation"},{"key":"48133_CR40","doi-asserted-by":"publisher","first-page":"9621","DOI":"10.1158\/0008-5472.CAN-10-1722","volume":"70","author":"J Webber","year":"2010","unstructured":"Webber, J., Steadman, R., Mason, M. D., Tabi, Z. & Clayton, A. Cancer exosomes trigger fibroblast to myofibroblast differentiation. Cancer research 70, 9621\u20139630, https:\/\/doi.org\/10.1158\/0008-5472.CAN-10-1722 (2010).","journal-title":"Cancer research"},{"key":"48133_CR41","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1158\/1078-0432.ccr-10-1489","volume":"17","author":"HG Zhang","year":"2011","unstructured":"Zhang, H. G. & Grizzle, W. E. Exosomes and cancer: a newly described pathway of immune suppression. Clinical cancer research: an official journal of the American Association for Cancer Research 17, 959\u2013964, https:\/\/doi.org\/10.1158\/1078-0432.ccr-10-1489 (2011).","journal-title":"Clinical cancer research: an official journal of the American Association for Cancer Research"},{"key":"48133_CR42","doi-asserted-by":"publisher","first-page":"671","DOI":"10.2217\/fon.13.222","volume":"10","author":"N Kosaka","year":"2014","unstructured":"Kosaka, N. et al. Dark side of the exosome: the role of the exosome in cancer metastasis and targeting the exosome as a strategy for cancer therapy. Future oncology (London, England) 10, 671\u2013681, https:\/\/doi.org\/10.2217\/fon.13.222 (2014).","journal-title":"Future oncology (London, England)"},{"key":"48133_CR43","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1158\/0008-5472.can-14-3225","volume":"75","author":"V Adorno-Cruz","year":"2015","unstructured":"Adorno-Cruz, V. et al. Cancer stem cells: targeting the roots of cancer, seeds of metastasis, and sources of therapy resistance. Cancer research 75, 924\u2013929, https:\/\/doi.org\/10.1158\/0008-5472.can-14-3225 (2015).","journal-title":"Cancer research"},{"key":"48133_CR44","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.canlet.2014.10.027","volume":"356","author":"L Zhao","year":"2015","unstructured":"Zhao, L., Liu, W., Xiao, J. & Cao, B. The role of exosomes and \u201cexosomal shuttle microRNA\u201d in tumorigenesis and drug resistance. Cancer letters 356, 339\u2013346, https:\/\/doi.org\/10.1016\/j.canlet.2014.10.027 (2015).","journal-title":"Cancer letters"},{"key":"48133_CR45","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1016\/s1470-2045(17)30621-6","volume":"18","author":"N van Zandwijk","year":"2017","unstructured":"van Zandwijk, N. et al. Safety and activity of microRNA-loaded minicells in patients with recurrent malignant pleural mesothelioma: a first-in-man, phase 1, open-label, dose-escalation study. The Lancet. Oncology 18, 1386\u20131396, https:\/\/doi.org\/10.1016\/s1470-2045(17)30621-6 (2017).","journal-title":"The Lancet. Oncology"},{"key":"48133_CR46","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.15252\/embr.201541930","volume":"17","author":"K Mukherjee","year":"2016","unstructured":"Mukherjee, K. et al. Reversible HuR-microRNA binding controls extracellular export of miR-122 and augments stress response. EMBO Rep 17, 1184\u20131203, https:\/\/doi.org\/10.15252\/embr.201541930 (2016).","journal-title":"EMBO Rep"},{"key":"48133_CR47","doi-asserted-by":"publisher","unstructured":"Guo, M. et al. Autologous tumor cell-derived microparticle-based targeted chemotherapy in lung cancer patients with malignant pleural effusion. Science translational medicine 11, https:\/\/doi.org\/10.1126\/scitranslmed.aat5690 (2019).","DOI":"10.1126\/scitranslmed.aat5690"},{"key":"48133_CR48","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1016\/0003-4975(95)00045-M","volume":"59","author":"HI Pass","year":"1995","unstructured":"Pass, H. I. et al. Characteristics of nine newly derived mesothelioma cell lines. The Annals of thoracic surgery 59, 835\u2013844 (1995).","journal-title":"The Annals of thoracic surgery"},{"key":"48133_CR49","first-page":"3199","volume":"47","author":"FR Reale","year":"1987","unstructured":"Reale, F. R. et al. Characterization of a human malignant mesothelioma cell line (H-MESO-1): a biphasic solid and ascitic tumor model. Cancer research 47, 3199\u20133205 (1987).","journal-title":"Cancer research"},{"key":"48133_CR50","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1158\/1078-0432.CCR-12-3202","volume":"19","author":"A Shukla","year":"2013","unstructured":"Shukla, A. et al. Extracellular signal-regulated kinase 5: a potential therapeutic target for malignant mesotheliomas. Clinical cancer research: an official journal of the American Association for Cancer Research 19, 2071\u20132083, https:\/\/doi.org\/10.1158\/1078-0432.CCR-12-3202 (2013).","journal-title":"Clinical cancer research: an official journal of the American Association for Cancer Research"},{"key":"48133_CR51","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1002\/ijc.25666","volume":"129","author":"JM Hillegass","year":"2011","unstructured":"Hillegass, J. M. et al. Increased efficacy of doxorubicin delivered in multifunctional microparticles for mesothelioma therapy. International journal of cancer 129, 233\u2013244, https:\/\/doi.org\/10.1002\/ijc.25666 (2011).","journal-title":"International journal of cancer"},{"key":"48133_CR52","doi-asserted-by":"publisher","first-page":"293","DOI":"10.18632\/oncotarget.22968","volume":"9","author":"JK Thompson","year":"2018","unstructured":"Thompson, J. K. et al. Extracellular signal regulated kinase 5 and inflammasome in progression of mesothelioma. Oncotarget 9, 293\u2013305, https:\/\/doi.org\/10.18632\/oncotarget.22968 (2018).","journal-title":"Oncotarget"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-48133-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-48133-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-48133-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T12:33:28Z","timestamp":1671280408000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-48133-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,12]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["48133"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-48133-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,12]]},"assertion":[{"value":"17 April 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 July 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 August 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"11688"}}