title: 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.
authors: Department of Laboratory Medicine, Changzheng Hospital, Shanghai, China.
authors: Xudong
authors: X
authors: Wang
authors: Chang
authors: C
authors: Li
authors: Shaoqing
authors: S
authors: Ju
authors: Yueguo
authors: Y
authors: Wang
authors: Huimin
authors: H
authors: Wang
authors: Renqian
authors: R
authors: Zhong
mesh_terms: D001853:Bone Marrow / Q000473:pathology; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D002448:Cell Adhesion; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D003907:Dexamethasone / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009101:Multiple Myeloma / Q000473:pathology*; D011719:Pyrazines / Q000494:pharmacology; D017154:Stromal Cells / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D001897:Boronic Acids; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone; D004317:Doxorubicin