Open Access

Essential role of microRNA-650 in the regulation of B-cell CLL/lymphoma 11B gene expression following transplantation: A novel mechanism behind the acute rejection of renal allografts

  • Authors:
    • Peng Jin
    • Hongxi Chen
    • Jinliang Xie
    • Cheng Zhou
    • Xiangrong Zhu
  • View Affiliations

  • Published online on: October 17, 2017     https://doi.org/10.3892/ijmm.2017.3194
  • Pages:1840-1850
  • Copyright: © Jin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Kidney transplantation is an effective final therapeutic procedure for patients with end-stage kidney failure. Although advanced immunosuppressive therapy is administered following transplantation, certain patients still suffer from acute allograft rejection. MicroRNAs (miRs) have a potential diagnostic and therapeutic value for acute renal allograft rejection; however, their underlying mechanism of action is largely unknown. In the present study, an increased level of miR-650 was identified to be associated with the downregulation of B-cell CLL/lymphoma 11B (BCL11B) expression in acute renal allograft rejection. Furthermore, in vitro study using human renal glomerular endothelial cells (HRGECs) transfected with a miR-650 mimic revealed that key characteristics of acute renal allograft rejection were observed, including apoptosis, the release of cytokines and the chemotaxis of macrophages, while the effects were reduced in HRGECs transfected with a miR-650 inhibitor. The existence of a conserved miR-650 binding site on the 3'-untranslated region of BCL11B mRNA was predicted by computational algorithms and confirmed by a luciferase reporter assay. Knockdown of BCL11B with small interfering RNA (siRNA) significantly increased the apoptotic rate and significantly decreased the proliferation ability of HRGECs compared with the negative control group. HRGECs transfected with a combination of BCL11B siRNA and the miR-650 mimic demonstrated a significant increase in the rate of apoptosis compared with the control. These results suggest that the upregulation of miR-650 contributes to the development of acute renal allograft rejection by suppression of BCL11B, which leads to apoptosis and inflammatory responses. Thus, miR-650 and BCL11B may represent potential therapeutic targets for the prevention of acute renal allograft rejection.

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December 2017
Volume 40 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

2016 Impact Factor: 2.341
Ranked #21/128 Medicine Research and Experimental
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APA
Jin, P., Chen, H., Xie, J., Zhou, C., & Zhu, X. (2017). Essential role of microRNA-650 in the regulation of B-cell CLL/lymphoma 11B gene expression following transplantation: A novel mechanism behind the acute rejection of renal allografts. International Journal of Molecular Medicine, 40, 1840-1850. https://doi.org/10.3892/ijmm.2017.3194
MLA
Jin, P., Chen, H., Xie, J., Zhou, C., Zhu, X."Essential role of microRNA-650 in the regulation of B-cell CLL/lymphoma 11B gene expression following transplantation: A novel mechanism behind the acute rejection of renal allografts". International Journal of Molecular Medicine 40.6 (2017): 1840-1850.
Chicago
Jin, P., Chen, H., Xie, J., Zhou, C., Zhu, X."Essential role of microRNA-650 in the regulation of B-cell CLL/lymphoma 11B gene expression following transplantation: A novel mechanism behind the acute rejection of renal allografts". International Journal of Molecular Medicine 40, no. 6 (2017): 1840-1850. https://doi.org/10.3892/ijmm.2017.3194