{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:21:54Z","timestamp":1772166114150,"version":"3.50.1"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T00:00:00Z","timestamp":1617148800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T00:00:00Z","timestamp":1617148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012502","name":"Collaborative Innovation Center for Water Treatment Technology and Materials","doi-asserted-by":"crossref","award":["(Project No. znpy2018034"],"award-info":[{"award-number":["(Project No. znpy2018034"]}],"id":[{"id":"10.13039\/501100012502","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["Grant No. 81870162"],"award-info":[{"award-number":["Grant No. 81870162"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Cell Int"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Myeloma bone disease (MBD) is a severe complication of\u00a0multiple myeloma (MM)\u00a0mainly due to an\u00a0imbalance between enhanced osteoclast activity\u00a0and reduced osteoblast function. Previous studies have demonstrated that miRNAs play a vital role\u00a0in the osteogenic differentiation of mesenchymal stromal cells (MSCs) in MM.\u00a0However, the value of miR\u2011302b in MBD remains to be further elucidated. The aim of this study is to explore the role of miR\u2011302b in the regulation of MBD osteogenic differentiation and evaluate the potential of a new therapeutic strategy for the clinical treatment of MBD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>Our previous research demonstrated that MiR-302b belongs to the miR-302 cluster and is able to inhibit tumor growth and osteolysis in an orthotopic osteosarcoma xenograft tumor mouse model. In this study, we first transfected miR-302b mimics, miR-302b inhibitor, and miR-302b NC into MM1.S and RPMI8226 MM cells to detect the correlation between miR-302b expression in the pathological specimens and the clinicopathological features by qPCR, the target correlation between miR-302b and DKK1 by immunohistochemistry, qPCR and Western blot, and the correlation between miR-302b and the Wnt\/\u03b2-catenin signaling pathway by Western blot.\u00a0The effect of miR-302b on osteoblastogenesis was also\u00a0studied in a subperiosteal tumorigenesis model of NOD\/SCID nude mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that increased miR-302b suppressed cell proliferation and induced cell apoptosis in RPMI 8226 and MM1.S cells. TargetScan online bioinformatic analysis predicted that miR-302b\u00a0is able to bind to 3\u2032UTR of DKK1 mRNA. Target binding of miR-302b to DKK1 was\u00a0demonstrated\u00a0by dual-luciferase reporter assay, qPCR, Western blot and immunohistochemistry,\u00a0indicating that\u00a0miR-302b\u00a0is able to degrade DKK1\u00a0in RPMI 8226 and MM1.S cells. The model of co-culturing MM cells with preosteoblast MC3T3-E1 cells showed that\u00a0miR-302b inhibits MM-induced suppression of osteoblast differentiation.\u00a0Western blotting showed\u00a0that miR-302b promotes\u00a0the\u00a0Wnt\/\u03b2-catenin signaling pathway in MM cells. Micro-CT and immunohistochemistry results showed that miR-302b\u00a0suppresses\u00a0myeloma bone destruction in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>miR-302b\u00a0is able to target\u00a0DKK1 and promote\u00a0the\u00a0Wnt\/\u03b2-catenin signaling pathway in MM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12935-021-01887-y","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T06:03:18Z","timestamp":1617170598000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Elevation of miR-302b prevents multiple myeloma cell growth and bone destruction by blocking DKK1 secretion"],"prefix":"10.1186","volume":"21","author":[{"given":"Zheyu","family":"Wu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yufeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiqiang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yufan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanlong","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuling","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3126-6429","authenticated-orcid":false,"given":"Lin","family":"Cai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,3,31]]},"reference":[{"issue":"2","key":"1887_CR1","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1038\/nrclinonc.2016.122","volume":"14","author":"S Manier","year":"2016","unstructured":"Manier S, Salem KZ, Park J, Landau DA, Getz G, Ghobrial IM. 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All of the specimens were obtained with the patients\u2019 informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"187"}}