{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:32:43Z","timestamp":1791325963887,"version":"4.3.1"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"35","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,9,2]]},"abstract":"<jats:p>\n                    Progress in understanding the biology of multiple myeloma (MM), a plasma cell malignancy, has been slow. The discovery of microRNAs (miRNAs), a class of small noncoding RNAs targeting multiple mRNAs, has revealed a new level of gene expression regulation. To determine whether miRNAs play a role in the malignant transformation of plasma cells (PCs), we have used both miRNA microarrays and quantitative real time PCR to profile miRNA expression in MM-derived cell lines (\n                    <jats:italic>n<\/jats:italic>\n                    = 49) and CD138+ bone marrow PCs from subjects with MM (\n                    <jats:italic>n<\/jats:italic>\n                    = 16), monoclonal gammopathy of undetermined significance (MGUS) (\n                    <jats:italic>n<\/jats:italic>\n                    = 6), and normal donors (\n                    <jats:italic>n<\/jats:italic>\n                    = 6). We identified overexpression of\n                    <jats:italic>miR-21<\/jats:italic>\n                    ,\n                    <jats:italic>miR-106b<\/jats:italic>\n                    \u223c\n                    <jats:italic>25<\/jats:italic>\n                    cluster,\n                    <jats:italic>miR-181a<\/jats:italic>\n                    and\n                    <jats:italic>b<\/jats:italic>\n                    in MM and MGUS samples with respect to healthy PCs. Selective up-regulation of\n                    <jats:italic>miR-32<\/jats:italic>\n                    and\n                    <jats:italic>miR-17<\/jats:italic>\n                    \u223c\n                    <jats:italic>92<\/jats:italic>\n                    cluster was identified in MM subjects and cell lines but not in MGUS subjects or healthy PCs. Furthermore, two miRNAs,\n                    <jats:italic>miR-19a<\/jats:italic>\n                    and\n                    <jats:italic>19b<\/jats:italic>\n                    , that are part of the\n                    <jats:italic>miR-17<\/jats:italic>\n                    \u223c\n                    <jats:italic>92<\/jats:italic>\n                    cluster, were shown to down regulate expression of SOCS-1, a gene frequently silenced in MM that plays a critical role as inhibitor of IL-6 growth signaling. We also identified p300-CBP-associated factor, a gene involved in p53 regulation, as a bona fide target of\n                    <jats:italic>the miR106b<\/jats:italic>\n                    \u223c\n                    <jats:italic>25<\/jats:italic>\n                    cluster,\n                    <jats:italic>miR-181a<\/jats:italic>\n                    and\n                    <jats:italic>b<\/jats:italic>\n                    , and\n                    <jats:italic>miR-32<\/jats:italic>\n                    . Xenograft studies using human MM cell lines treated with\n                    <jats:italic>miR-19a<\/jats:italic>\n                    and\n                    <jats:italic>b<\/jats:italic>\n                    , and\n                    <jats:italic>miR-181a<\/jats:italic>\n                    and\n                    <jats:italic>b<\/jats:italic>\n                    antagonists resulted in significant suppression of tumor growth in nude mice. In summary, we have described a MM miRNA signature, which includes miRNAs that modulate the expression of proteins critical to myeloma pathogenesis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0806202105","type":"journal-article","created":{"date-parts":[[2008,8,26]],"date-time":"2008-08-26T20:45:01Z","timestamp":1219783501000},"page":"12885-12890","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":467,"title":["MicroRNAs regulate critical genes associated with multiple myeloma pathogenesis"],"prefix":"10.1073","volume":"105","author":[{"given":"Flavia","family":"Pichiorri","sequence":"first","affiliation":[{"name":"Departments of *Molecular Virology, Immunology, and Human Genetics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Suk","family":"Suh","sequence":"additional","affiliation":[{"name":"Departments of *Molecular Virology, Immunology, and Human Genetics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Ladetto","sequence":"additional","affiliation":[{"name":"Division of Hematology, University of Torino, 10126 Torino, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kuehl","sequence":"additional","affiliation":[{"name":"Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20889-5105; 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