Loss of Reelin suppresses cell survival and mobility in non-Hodgkin lymphoma

  • Authors:
    • Aixia Dou
    • Zhilun Wang
    • Ni Zhang
    • Junli Liu
  • View Affiliations

  • Published online on: May 4, 2017     https://doi.org/10.3892/or.2017.5626
  • Pages: 3572-3580
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Abstract

Reelin, a secreted glycoprotein, was recently demonstrated to be involved in the pathogenesis of cancer. However, its oncogenic activities in non-Hodgkin lymphoma (NHL) remain unclear. Therefore, we aimed to evaluate the functional role of reelin in NHL, and the underlying molecular mechanisms. In the present study, we analyzed reelin expression in lymphoma tissues and cell lines using immunohistochemistry, immunofluorescence staining, qRT-PCR and western blotting. Then, the expression of Reelin was silenced with short hairpin RNA (shRNA)-expressing plasmid in the NHL cell line A20. The effects of Reelin depletion on cell growth, migration and invasion in vitro were determined by CCK-8 and transwell assays. Flow cytometry was used to examine the cell cycle status and cellular apoptosis. Hoechst 33258 fluorescence staining was used to analyze morphologic changes caused by apoptosis. The second messenger, cAMP was analyzed by ELISA. In addition, we used nude mice to evaluate the tumorigenic ability of reelin. Aberrant upregulated levels of mRNA and protein of reelin were observed in lymphoma tissues and cell lines. Knockdown of reelin suppressed lymphoma growth, migration and invasion ability of A20. Furthermore, reelin depletion induced cell cycle arrest in G0/G1 phase and promoted apoptosis of A20 cells. Further analysis indicated that knockdown of reelin downregulated the expression of CDK5 and IL-10 and activated caspase-3 in shReelin group. ELISA assay showed cAMP at a lower level in shReelin group. SQ22536, a cAMP pathway inhibitor, treated A20 cells and revealed likely effects. The tumor size in a mouse model injected shReelin was significantly smaller than controls. There results suggest that reelin played essential roles in the development of lymphoma and might be a potential drug target in lymphoma.
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June-2017
Volume 37 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Dou A, Wang Z, Zhang N and Liu J: Loss of Reelin suppresses cell survival and mobility in non-Hodgkin lymphoma. Oncol Rep 37: 3572-3580, 2017
APA
Dou, A., Wang, Z., Zhang, N., & Liu, J. (2017). Loss of Reelin suppresses cell survival and mobility in non-Hodgkin lymphoma. Oncology Reports, 37, 3572-3580. https://doi.org/10.3892/or.2017.5626
MLA
Dou, A., Wang, Z., Zhang, N., Liu, J."Loss of Reelin suppresses cell survival and mobility in non-Hodgkin lymphoma". Oncology Reports 37.6 (2017): 3572-3580.
Chicago
Dou, A., Wang, Z., Zhang, N., Liu, J."Loss of Reelin suppresses cell survival and mobility in non-Hodgkin lymphoma". Oncology Reports 37, no. 6 (2017): 3572-3580. https://doi.org/10.3892/or.2017.5626