miRNA-202 in bone marrow stromal cells affects the growth and adhesion of multiple myeloma cells by regulating B cell-activating factor

Clin Exp Med. 2016 Aug;16(3):307-16. doi: 10.1007/s10238-015-0355-4. Epub 2015 May 14.

Abstract

Bone marrow stromal cells (BMSCs) up-regulate B cell-activating factor (BAFF) in multiple myeloma. Increasing experimental evidence has shown that microRNAs play a causal role in hematology tumorigenesis. In this study, we characterized the role of miR-202 in regulating the expression of BAFF in BMSCs. It was found that expressions of BAFF mRNA and protein were increased in BMSCs treated with miR-202 inhibitor. The growth rate of miR-202 mimics transfection cells was significantly lower than that of non-transfected cells. The expression of Bcl-2 protein was down-regulated, and Bax protein was up-regulated after miR-202 mimics transfection. Over-expression of miR-202 in BMSCs rendered MM cells more sensitive to bortezomib. More significantly, the regulatory effect of miR-202 could inhibit the activation of NF-κB pathway in BMSCs. These results suggest that miR-202 functions as a modulator that can negatively regulate BAFF by inhibiting MM cell survival, growth, and adhesion in the bone marrow microenvironment.

Keywords: B cell-activating factor (BAFF); Bone marrow stromal cells (BMSCs); Drug resistance; Multiple myeloma (MM); microRNA-202 (miR-202).

MeSH terms

  • Aged
  • B-Cell Activating Factor / metabolism*
  • B-Lymphocytes / physiology*
  • Cell Adhesion*
  • Cell Proliferation*
  • Cyclins / analysis
  • Female
  • Gene Expression Profiling
  • Humans
  • Male
  • Mesenchymal Stem Cells / metabolism*
  • MicroRNAs / metabolism*
  • Middle Aged
  • Multiple Myeloma / pathology*
  • bcl-2-Associated X Protein / analysis

Substances

  • B-Cell Activating Factor
  • BAX protein, human
  • Cyclins
  • MIRN202 microRNA, human
  • MicroRNAs
  • TNFSF13B protein, human
  • bcl-2-Associated X Protein