HSPH1 inhibition downregulates Bcl-6 and c-Myc and hampers the growth of human aggressive B-cell non-Hodgkin lymphoma
HSPH1 inhibition downregulates Bcl-6 and c-Myc and hampers the growth of human aggressive B-cell non-Hodgkin lymphoma
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DOI：
10.1182/blood-2014-07-590034
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发表时间：
2015-03-12
期刊：
影响因子：
20.3
通讯作者：
Di Nicola, Massimo
中科院分区：
文献类型：
--
作者：
Zappasodi, Roberta;Ruggiero, Giusi;Di Nicola, Massimo
我们已经表明，人类B细胞非霍奇金淋巴瘤（B-NHL）表达热休克蛋白（HSP）H1/105在其侵略性的功能。在这里，我们现在澄清它作为一个功能性B-NHL的目标，通过测试的假设，它促进了关键的淋巴瘤癌蛋白的稳定。Bcl-6和c-Myc下调可逆转4种侵袭性B-NHL模型中HSPH 1的沉默。HSPH 1沉默的Namalwa细胞的体外和体内分析表明，这种效果与显着的生长延迟和致瘤性的损失时，10 - 4细胞注射到小鼠。有趣的是，我们发现HSPH 1在Namalwa细胞和原发性侵袭性B-NHL中与c-Myc和Bcl-6发生物理相互作用。因此，在这些疾病中，HSPH 1和c-Myc或Bcl-6的表达呈正相关。我们的研究表明，HSPH 1同时有利于2个关键的淋巴瘤癌蛋白的表达，从而证实了其作为侵袭性B-NHL的有价值的治疗靶点的候选资格。
We have shown that human B-cell non-Hodgkin lymphomas (B-NHLs) express heat shock protein (HSP) H1/105 in function of their aggressiveness. Here, we now clarify its role as a functional B-NHL target by testing the hypothesis that it promotes the stabilization of key lymphoma oncoproteins. HSPH1 silencing in 4 models of aggressive B-NHLs was paralleled by Bcl-6 and c-Myc downregulation. In vitro and in vivo analysis of HSPH1-silenced Namalwa cells showed that this effect was associated with a significant growth delay and the loss of tumorigenicity when 10 4 cells were injected into mice. Interestingly, we found that HSPH1 physically interacts with c-Myc and Bcl-6 in both Namalwa cells and primary aggressive B-NHLs. Accordingly, expression of HSPH1 and either c-Myc or Bcl-6 positively correlated in these diseases. Our study indicates that HSPH1 concurrently favors the expression of 2 key lymphoma oncoproteins, thus confirming its candidacy as a valuable therapeutic target of aggressive B-NHLs.