Epstein–Barr virus latent membrane protein-1 protects B-cell lymphoma from rituximab-induced apoptosis through miR-155-mediated Akt activation and up-regulation of Mcl-1

Abstract

Rituximab is a CD20-targeted monoclonal antibody widely used in the treatment of B-cell lymphoma. Previously, we have shown that Epstein–Barr virus (EBV) latent membrane protein-1 (LMP1) increases chemoresistance in malignant cancer cells. In this study we examined the effects of LMP1 on the response of B-cell lymphoma cell lines to rituximab. Here we show for the first time that LMP1 activates the Akt pathway and up-regulates Mcl-1 through miR-155 expression, which contributes to the survival of rituximab-treated B-cell lymphoma cells. Furthermore, Akt inhibition or knockdown of Mcl-1 and miR-155 was found to be an efficient strategy to overcome rituximab resistance caused by LMP1 expression. Thus, we propose Akt and Mcl-1 and miR-155 as molecular targets for therapeutic intervention in the treatment of EBV-associated B-cell lymphoma with rituximab.

Keywords::

• LMP1
• B-cell lymphoma
• rituximab resistance

Acknowledgements

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2011-0010951) and Samsung Biomedical Research Institute (C-A6-208-3).

Potential conflict of interest

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