J Cancer 2015; 6(10):953-961. doi:10.7150/jca.12067

Research Paper

Loss of IRF8 Inhibits the Growth of Diffuse Large B-cell Lymphoma

Yulian Xu1*, Lei Jiang1*, Jianchen Fang2, Rong Fang1, Herbert C. Morse III3, Guifang Ouyang4, Jeff X. Zhou1✉

1. Department of Pathology, Ningbo University School of Medicine, Ningbo, Zhejiang, China
2. The Pathology Service Center, Ningbo, Zhejiang, China
3. The National Institute of Allergy and Infectious Diseases, the National Institutes of Health, Rockville, MD, USA
4. Department of Hematology, Ningbo University Affiliated First Hospital, Ningbo, Zhejiang, China
* These authors contributed equally to this work.

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Xu Y, Jiang L, Fang J, Fang R, Morse HC III, Ouyang G, Zhou JX. Loss of IRF8 Inhibits the Growth of Diffuse Large B-cell Lymphoma. J Cancer 2015; 6(10):953-961. doi:10.7150/jca.12067. Available from http://www.jcancer.org/v06p0953.htm

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IRF8 is a transcription factor with a critical role in B lymphocyte development and functions. Its role in human diffuse large B-cell lymphoma (DLBCL), however, remained elusive. In this study, using shRNA-mediated knockdown of IRF8 expression, we found that the loss of IRF8 significantly reduced the proliferation of DLBCL cells (P<0.05). Mechanistically, decreasing the levels of IRF8 led to a suppression of the phosphorylation of p38 and ERK, molecules critical for B cell proliferation. Furthermore, using a xenograft lymphoma mouse model, we found that the loss of IRF8 significantly inhibited the growth of lymphomas in vivo (P<0.05). Immunohistochemical analysis of human DLBCL tissues revealed that the levels of IRF8 were significantly greater in non-germinal center B-cell-like (non-GCB) subtype than that in GCB subtype (P<0.05). Analysis of public available data also suggested that the expression levels of IRF8 mRNA in human DLBCL tissues were inversely correlated with patients' overall survival time. Taken together, this study suggested that IRF8 may play an oncogenic role in human DLBCL by promoting cell proliferation.

Keywords: lymphoma, IRF8, DLBCL