American Association for Cancer Research
10780432ccr123325-sup-fig3.pdf (544.87 kB)

Supplementary Figure 3 from Targeting miR-21 Inhibits In Vitro and In Vivo Multiple Myeloma Cell Growth

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journal contribution
posted on 2023-03-31, 17:45 authored by Emanuela Leone, Eugenio Morelli, Maria T. Di Martino, Nicola Amodio, Umberto Foresta, Annamaria Gullà, Marco Rossi, Antonino Neri, Antonio Giordano, Nikhil C. Munshi, Kenneth C. Anderson, Pierosandro Tagliaferri, Pierfrancesco Tassone

PDF file - 544K, Figure S3. Endogenous expression of miR-21 inhibitors decreases miR-21 levels.



Purpose: Deregulated expression of miRNAs plays a role in the pathogenesis and progression of multiple myeloma. Among upregulated miRNAs, miR-21 has oncogenic potential and therefore represents an attractive target for the treatment of multiple myeloma.Experimental Design: Here, we investigated the in vitro and in vivo anti-multiple myeloma activity of miR-21 inhibitors.Results: Either transient-enforced expression or lentivirus-based constitutive expression of miR-21 inhibitors triggered significant growth inhibition of primary patient multiple myeloma cells or interleukin-6–dependent/independent multiple myeloma cell lines and overcame the protective activity of human bone marrow stromal cells. Conversely, transfection of miR-21 mimics significantly increased proliferation of multiple myeloma cells, showing its tumor-promoting potential in multiple myeloma. Importantly, upregulation of miR-21 canonical validated targets (PTEN, Rho-B, and BTG2), together with functional impairment of both AKT and extracellular signal–regulated kinase signaling, were achieved by transfection of miR-21 inhibitors into multiple myeloma cells. In vivo delivery of miR-21 inhibitors in severe combined immunodeficient mice bearing human multiple myeloma xenografts expressing miR-21induced significant antitumor activity. Upregulation of PTEN and downregulation of p-AKT were observed in retrieved xenografts following treatment with miR-21 inhibitors.Conclusion: Our findings show the first evidence that in vivo antagonism of miR-21 exerts anti-multiple myeloma activity, providing the rationale for clinical development of miR-21 inhibitors in this still incurable disease. Clin Cancer Res; 19(8); 2096–106. ©2013 AACR.

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