Xu Yulian, Jiang Lei, Fang Jianchen, Fang Rong, Morse Herbert C, Ouyang Guifang, Zhou Jeff X
1. Department of Pathology, Ningbo University School of Medicine, Ningbo, Zhejiang, China.
2. The Pathology Service Center, Ningbo, Zhejiang, China.
J Cancer. 2015 Aug 7;6(10):953-61. doi: 10.7150/jca.12067. eCollection 2015.
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.
IRF8是一种转录因子，在B淋巴细胞发育和功能中起关键作用。然而，其在人类弥漫性大B细胞淋巴瘤（DLBCL）中的作用仍不清楚。在本研究中，我们使用shRNA介导的IRF8表达敲低，发现IRF8的缺失显著降低了DLBCL细胞的增殖（P<0.05）。机制上，降低IRF8水平导致对B细胞增殖至关重要的分子p38和ERK的磷酸化受到抑制。此外，使用异种移植淋巴瘤小鼠模型，我们发现IRF8的缺失显著抑制了体内淋巴瘤的生长（P<0.05）。对人类DLBCL组织的免疫组织化学分析显示，非生发中心B细胞样（non-GCB）亚型中IRF8的水平显著高于生发中心B细胞（GCB）亚型（P<0.05）。对公开可用数据的分析还表明人类DLBCL组织中IRF8 mRNA的表达水平与患者的总生存时间呈负相关。综上所述，本研究表明IRF8可能通过促进细胞增殖在人类DLBCL中发挥致癌作用。
