Myeloma cell adhesion to bone marrow stromal cells confers drug resistance by microRNA-21 up-regulation

Abstract

The bone marrow microenvironment plays a role in myeloma cell proliferation and adhesion-mediated drug resistance. In this study, we investigated microRNA-21 (miR-21) expression changes in myeloma cells that adhered to bone marrow stromal cells (BMSCs). In addition, we studied the synergistic effect of miR-21 inhibition with dexamethasone (Dex), doxorubicin (Dox), or bortezomib (Bort) on myeloma cell survival. We found that up-regulation of miR-21 expression was partially driven by nuclear factor-κB (NF-κB) signaling via myeloma cell adhesion to BMSCs. We also confirmed that RhoB is a miR-21 regulation target gene. Moreover, miR-21 inhibition combined with cytotoxic drug Dex or Dox inhibited myeloma cell survival more effectively than either treatment alone. These results suggest that the regulatory mechanisms of miR-21 expression may be a promising target for fine-tuning anti-myeloma therapy.

Keywords:

• Multiple myeloma (MM)
• microRNA-21 (miR-21)
• bone marrow microenvironment
• drug resistance

Acknowledgement

We thank Dr. Jianfei Huang (Department of Pathology of the Affiliated Hospital of Nantong University) for assistance with the luciferase reporter assay.

Potential conflict of interest:

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