Loss of IRF8 Inhibits the Growth of Diffuse Large B-cell Lymphoma.
Loss of IRF8 Inhibits the Growth of Diffuse Large B-cell Lymphoma.
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IRF8 缺失可抑制弥漫性大 B 细胞淋巴瘤的生长
DOI：
10.7150/jca.12067
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发表时间：
2015
影响因子：
3.9
通讯作者：
Zhou JX
中科院分区：
文献类型：
--
作者：
Xu Y;Jiang L;Fang J;Fang R;Morse HC 3rd;Ouyang G;Zhou JX
IRF 8是在B淋巴细胞发育和功能中具有关键作用的转录因子。然而，它在人类弥漫性大B细胞淋巴瘤（DLBCL）中的作用仍然难以捉摸。在本研究中，我们利用shRNA介导的IRF 8表达的敲低，发现IRF 8的缺失显著降低DLBCL细胞的增殖（P<0.05）。从机制上讲，降低IRF 8的水平导致对B细胞增殖至关重要的p38和ERK的磷酸化的抑制。此外，使用异种移植淋巴瘤小鼠模型，我们发现IRF 8的缺失显著抑制体内淋巴瘤的生长（P<0.05）。免疫组化结果显示，非生殖中心B细胞样（non-GCB）型DLBCL组织中IRF 8的表达明显高于GCB型（P<0.05）。对公开数据的分析还表明，人DLBCL组织中IRF 8 mRNA的表达水平与患者的总生存时间呈负相关。总之，这项研究表明，IRF 8可能通过促进细胞增殖在人DLBCL中发挥致癌作用。
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.