Yin Yang 1 overexpression in diffuse large B-cell lymphoma is associated with B-cell transformation and tumor progression
Yin Yang 1 overexpression in diffuse large B-cell lymphoma is associated with B-cell transformation and tumor progression
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DOI：
10.4161/cc.9.3.10554
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发表时间：
2010-02-01
期刊：
影响因子：
4.3
通讯作者：
Libra, Massimo
中科院分区：
文献类型：
--
作者：
Castellano, Giancarlo;Torrisi, Elena;Libra, Massimo
阴阳1 （YY1）是一种多功能转录因子，已被证明参与多种癌症的发病机制。然而，其在血液恶性肿瘤中的作用尚未得到充分的研究。在本研究中，我们使用计算方法发现，与低级别淋巴瘤和正常b细胞相比，YY1转录物水平在包括Burkitt淋巴瘤和弥漫大b细胞淋巴瘤（DLBCL）在内的高级别淋巴瘤中均显著升高。基因表达的显著增加导致三种NHL细胞系蛋白水平的显著增加。YY1的表达与DLBCL的一些临床病理特征相关，表明高水平的YY1 mRNA与高水平的BCL-6蛋白呈正相关。此外，通过分析Hummel数据集中的DLBCL大序列，我们在与YY1正相关的前50个基因中确定了转录因子PAX-5。这些发现也得到了生物网络分析的支持，其中与DLBCL中YY1表达水平相关的得分最高的网络是细胞运动、血液系统发育和功能以及免疫反应。总的来说，这些数据表明YY1参与B细胞转化，通过B细胞正常发育的失调影响细胞周期和细胞运动而导致高级别淋巴瘤。
Yin Yang 1 (YY1), a multifunctional transcription factor, has been shown to be involved in the pathogenesis of several cancer types. However, its role in hematological malignancies has not yet been fully investigated. In the present study, using computational methods, we showed that YY1 transcript levels were significantly increased in the high-grade lymphomas, including Burkitt's lymphoma and diffuse large B-cell lymphoma (DLBCL), compared with those of both low-grade lymphomas and normal B-cells. The significant increase in gene expression resulted in a significant increase also at protein level in three NHL cell lines. The association of YY1 expression with some clinical-pathological features in DLBCL showed a positive correlation between a high level of YY1 mRNA and high levels of BCL-6 protein. Moreover, by analyzing the large series of DLBCL in the Hummel dataset, we identified the transcription factor PAX-5 among the top 50 genes positively correlated with YY1. These findings are also supported by the biological network analysis in which the top network, with the highest score, associated with YY1 expression levels in DLBCL is cellular movement, hematological system development and function, and immune response. Overall these data suggest that YY1 is involved in B cells transformation which gives rise to high-grade lymphomas through a dysregulation in the normal development of B cells affecting cell cycle and cellular motility.