{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T14:13:05Z","timestamp":1786889585578,"version":"build-2736575974"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T00:00:00Z","timestamp":1642723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Multiple myeloma (MM) progression and drug resistance depend on the crosstalk between MM cells and bone marrow (BM) fibroblasts (FBs). During monoclonal gammopathy of undetermined significance (MGUS) to MM transition, MM cell\u2010derived exosomes (EXOs) reprogram the miRNA (miR) profile of FBs, inducing the overexpression miR\u201023b\u20103p, miR\u201027b\u20103p, miR\u2010125b\u20105p, miR\u2010214\u20103p, and miR\u20105100. Here, we demonstrate that the miR content of MM FB\u2010derived EXOs (FB\u2010EXOs) overlaps the miR profile of parental FBs by overexpressing comparable levels of miR\u201023b\u20103p, miR\u201027b\u20103p, miR\u2010125b\u20105p, miR\u2010214\u20103p, and miR\u20105100. Recipient MM cells co\u2010cultured with MM FB\u2010EXOs selectively overexpress only miR\u2010214\u20103p and miR\u20105100 but not miR\u201023b\u20103p, miR\u201027b\u20103p, and miR\u2010125b\u20105p, suggesting a putative selective transfer. MM cells express\n                    <jats:italic>HOTAIR<\/jats:italic>\n                    ,\n                    <jats:italic>TOB1\u2010AS1<\/jats:italic>\n                    , and\n                    <jats:italic>MALAT1<\/jats:italic>\n                    lncRNAs. Transient transfection of MM cells with lnc\u00b7siRNAs demonstrates that\n                    <jats:italic>HOTAIR<\/jats:italic>\n                    ,\n                    <jats:italic>TOB1\u2010AS1<\/jats:italic>\n                    , and\n                    <jats:italic>MALAT1<\/jats:italic>\n                    lncRNAs are sponges for miR\u201023b\u20103p, miR\u201027b\u20103p, and miR\u2010125b\u20105p. Indeed, lncRNA knockdown significantly increased miR levels in U266\u2009MM cells co\u2010cultured with MM FB\u2010EXOs. Selective miR\u2010214\u20103p and miR\u20105100 overexpression modulates MAPK, PI3K\/AKT\/mTOR, and p53 pathways in MM cells. Interrogation using the DIANA tools algorithm and transient overexpression using miR mimic probes confirmed the involvement of miR\u2010214\u20103p and miR\u20105100 and their target genes,\n                    <jats:italic>PTEN<\/jats:italic>\n                    and\n                    <jats:italic>DUSP16<\/jats:italic>\n                    , respectively, in the modulation of these intracellular pathways. Finally, the uptake of EXOs as well as miR\u2010214\u20103p and miR\u20105100 overexpression increase MM cell proliferation and resistance to bortezomib\u2010induced apoptosis by switching the balance between pro\u2010\/anti\u2010apoptotic proteins. Overall, these data show that MM cells are not simply a container into which EXOs empty their cargo. On the contrary, tumour cells finely neutralize exosomal miRs via lncRNA expression to ensure their survival. \u00a9 2021 The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.5852","type":"journal-article","created":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T11:32:22Z","timestamp":1639654342000},"page":"402-413","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Myeloma cells regulate\n                    <scp>miRNA<\/scp>\n                    transfer from fibroblast\u2010derived exosomes by expression of\n                    <scp>lncRNAs<\/scp>"],"prefix":"10.1002","volume":"256","author":[{"given":"Ilaria","family":"Saltarella","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology, Unit of Internal Medicine \u2018Guido Baccelli\u2019 University of Bari Medical School  Bari 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Medical School  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assunta","family":"Melaccio","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology, Unit of Internal Medicine \u2018Guido Baccelli\u2019 University of Bari Medical School  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Curci","sequence":"additional","affiliation":[{"name":"Unit of Hematology and Stem Cell Transplantation AOUC Policlinico  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Annese","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Neurosciences and Sensory Organs, Section of Human Anatomy and Histology University of Bari Medical School  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Nico","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Neurosciences and Sensory Organs, Section of Human Anatomy and Histology University of Bari Medical School  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Giovanni","family":"Solimando","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology, Unit of Internal Medicine \u2018Guido Baccelli\u2019 University of Bari Medical School  Bari Italy"},{"name":"IRCCS Istituto Tumori \u2018Giovanni Paolo II\u2019  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Bartoli","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology, Unit of Internal Medicine \u2018Guido Baccelli\u2019 University of Bari Medical School  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doron","family":"Tolomeo","sequence":"additional","affiliation":[{"name":"Department of Biology University of Bari \u2018Aldo 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