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

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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.

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Abbreviations

miRNA:

microRNA

BMSCs:

Bone marrow stromal cells

MM:

Multiple myeloma

BAFF:

B cell-activating factor

Bort:

Bortezomib

Thal:

Thalidomide

Dex:

Dexamethasone

TNF:

Tumor necrosis factors

PBMCs:

Peripheral blood mononuclear cells

CAM-DR:

Cell adhesion-mediated drug resistance

ICAM-1:

Intercellular adhesion molecule-1

VCAM-1:

Vascular cell adhesion molecule-1

VEGF:

Vascular endothelial growth factor

IL-6:

Interleukin 6

ELISA:

Enzyme-linked immunosorbent assay

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Acknowledgments

Grant support: the National Natural Science Foundation of China (81301498; 81271920); Jiangsu Provincial Program for Medical Innovation Teams and Leading Talents (LJ201133); Scientific Research Subject of Jiangsu Province Health Department (H201422), and the six major human resources project of Jiangsu Province (20012-WS-119), Translational Medicine Project of Affiliated Hospital of Nantong University (TDF-zh201407).

Conflict of interest

The authors have no conflicts of interests.

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Authors and Affiliations

  1. Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, #20 Xisi Road, Nantong, 226001, JS, People’s Republic of China

    Xianjuan Shen, Jing Qi, Wei Shi, Xinhua Wu & Shaoqing Ju

  2. Nantong University, #9 Seyuan Road, Nantong, 226001, JS, People’s Republic of China

    Yuehua Guo & Shaoqing Ju

  3. The First Hospital Affiliated to Soochow University, #20 Shizi Road, Suzhou, 215006, JS, People’s Republic of China

    Jiajia Yu

  4. Laboratory Medicine Center, Affiliated Hospital of Nantong University, #20 Xisi Road, Nantong, 226001, JS, People’s Republic of China

    Hongbing Ni & Shaoqing Ju

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  1. Xianjuan Shen
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  2. Yuehua Guo
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  3. Jiajia Yu
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  4. Jing Qi
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Correspondence to Shaoqing Ju.

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Shen, X., Guo, Y., Yu, J. et al. 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 16, 307–316 (2016). https://doi.org/10.1007/s10238-015-0355-4

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  • DOI: https://doi.org/10.1007/s10238-015-0355-4

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