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首页> 外文期刊>Molecular Cancer >SOX11 expression correlates to promoter methylation and regulates tumor growth in hematopoietic malignancies
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SOX11 expression correlates to promoter methylation and regulates tumor growth in hematopoietic malignancies

机译：SOX11表达与启动子甲基化相关，并调节造血系统恶性肿瘤中的肿瘤生长

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Background The transcription factor SOX11 plays an important role in embryonic development of the central nervous system (CNS) and is expressed in the adult immature neuron but is normally not expressed in any other adult tissue. It has recently been reported to be implicated in various malignant neoplasms, including several lymphoproliferative diseases, by its specific expression and in some cases correlation to prognosis. SOX11 has been shown to prevent gliomagenesis in vivo but the causes and consequences of aberrant expression of SOX11 outside the CNS remain unexplained. Results We now show the first function of SOX11 in lymphoproliferative diseases, by demonstrating in vitro its direct involvement in growth regulation, as assessed by siRNA -mediated silencing and ectopic overexpression in hematopoietic malignancies. Gene Chip analysis identified cell cycle regulatory pathways, including Rb-E2F, to be associated with SOX11-induced growth reduction. Furthermore, promoter analysis revealed that SOX11 is silenced through DNA methylation in B cell lymphomas, suggesting that its regulation is epigenetically controlled. Conclusions The data show that SOX11 is not a bystander but an active and central regulator of cellular growth, as both siRNA -mediated knock-down and ectopic overexpression of SOX11 resulted in altered proliferation. Thus, these data demonstrate a tumor suppressor function for SOX11 in hematopoietic malignancies and revealed a potential epigenetic regulation of this developmentally involved gene.
机译：背景技术转录因子SOX11在中枢神经系统（CNS）的胚胎发育中起重要作用，并在成年未成熟神经元中表达，但通常在任何其他成年组织中均不表达。最近据报道，它的特异性表达以及与预后的相关性与多种恶性肿瘤有关，包括几种淋巴增生性疾病。已经显示出SOX11可以在体内预防神经胶质瘤的发生，但是尚无法解释中枢神经系统外SOX11异常表达的原因和后果。结果现在我们通过在体外证明SOX11在淋巴增生性疾病中的第一个功能，通过在siRNA介导的沉默和异位过表达在造血系统恶性肿瘤中进行评估来证明其直接参与了生长调节。基因芯片分析确定了细胞周期调控途径，包括Rb-E2F，与SOX11诱导的生长减少有关。此外，启动子分析显示SOX11通过B细胞淋巴瘤中的DNA甲基化而沉默，这表明它的调控是表观遗传的。结论数据表明，SOX11不是旁观者，而是细胞生长的活跃和中央调节者，因为siRNA介导的敲低和异位过表达SOX11都会导致增殖改变。因此，这些数据证明了SOX11在造血系统恶性肿瘤中具有抑癌功能，并揭示了该发育相关基因的潜在表观遗传调控。

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