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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Blotting, Western, Cell Line, Tumor, Cell Proliferation, Cell Survival, Cells, Cultured, Extracellular Signal-Regulated MAP Kinases, Gene Expression Regulation, Neoplastic, Humans, Immediate-Early Proteins, Male, Mice, Mice, SCID, MicroRNAs, Multiple Myeloma, PTEN Phosphohydrolase, Proto-Oncogene Proteins c-akt, RNA, Antisense, Reverse Transcriptase Polymerase Chain Reaction, Transfection, Tumor Cells, Cultured, Tumor Suppressor Proteins, Xenograft Model Antitumor Assays, rhoB GTP-Binding Protein.
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Does targeting miR-21 inhibit in vitro and in vivo multiple myeloma cell growth? Context: 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. Here, we investigated the in vitro and in vivo anti-multiple myeloma activity of miR-21 inhibitors. 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-21 induced significant antitumor activity. Upregulation of PTEN and downregulation of p-AKT were observed in retrieved xenografts following treatment with miR-21 inhibitors.
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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. Final Decision: yes