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- W4361944322 abstract "<div>Abstract<p><b>Purpose:</b> Deregulated expression of miRNAs has been shown in multiple myeloma (MM). A promising strategy to achieve a therapeutic effect by targeting the miRNA regulatory network is to enforce the expression of miRNAs that act as tumor suppressor genes, such as miR-34a.</p><p><b>Experimental Design:</b> Here, we investigated the therapeutic potential of synthetic miR-34a against human MM cells <i>in vitro</i> and <i>in vivo</i>.</p><p><b>Results:</b> Either transient expression of miR-34a synthetic mimics or lentivirus-based miR-34a-stable enforced expression triggered growth inhibition and apoptosis in MM cells <i>in vitro</i>. Synthetic miR-34a downregulated canonic targets BCL2, CDK6, and NOTCH1 at both the mRNA and protein level. Lentiviral vector-transduced MM xenografts with constitutive miR-34a expression showed high growth inhibition in severe combined immunodeficient (SCID) mice. The anti-MM activity of lipidic-formulated miR-34a was further shown <i>in vivo</i> in two different experimental settings: (i) SCID mice bearing nontransduced MM xenografts; and (ii) SCID-<i>synth-hu</i> mice implanted with synthetic 3-dimensional scaffolds reconstituted with human bone marrow stromal cells and then engrafted with human MM cells. Relevant tumor growth inhibition and survival improvement were observed in mice bearing TP53-mutated MM xenografts treated with miR-34a mimics in the absence of systemic toxicity.</p><p><b>Conclusions:</b> Our findings provide a proof-of-principle that formulated synthetic miR-34a has therapeutic activity in preclinical models and support a framework for development of miR-34a–based treatment strategies in MM patients. <i>Clin Cancer Res; 18(22); 6260–70. ©2012 AACR</i>.</p></div>" @default.
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- W4361944322 date "2023-03-31" @default.
- W4361944322 modified "2023-09-26" @default.
- W4361944322 title "Data from Synthetic miR-34a Mimics as a Novel Therapeutic Agent for Multiple Myeloma: <i>In Vitro</i> and <i>In Vivo</i> Evidence" @default.
- W4361944322 doi "https://doi.org/10.1158/1078-0432.c.6520806" @default.
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