Department of Immunotechnology, Lund University, Lund, Sweden.
Mol Cancer. 2010 Jul 12;9:187. doi: 10.1186/1476-4598-9-187.
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.
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.
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.
转录因子 SOX11 在中枢神经系统（CNS）的胚胎发育中起着重要作用，在成年未成熟神经元中表达，但在其他任何成年组织中均不表达。最近有报道称，它通过其特异性表达并在某些情况下与预后相关，参与了各种恶性肿瘤，包括几种淋巴增生性疾病。SOX11 已被证明可在体内预防神经胶质瘤的发生，但 CNS 外 SOX11 异常表达的原因和后果仍未得到解释。
我们现在通过证明其在造血恶性肿瘤中通过 siRNA 介导的沉默和异位过表达直接参与生长调节，首次展示了 SOX11 在淋巴增生性疾病中的功能。基因芯片分析确定了细胞周期调节途径，包括 Rb-E2F，与 SOX11 诱导的生长减少有关。此外，启动子分析表明，SOX11 通过 B 细胞淋巴瘤中的 DNA 甲基化被沉默，提示其调节受表观遗传控制。
这些数据表明，SOX11 不是旁观者，而是细胞生长的主动和核心调节剂，因为 siRNA 介导的敲低和 SOX11 的异位过表达都会导致增殖改变。因此，这些数据表明 SOX11 在造血恶性肿瘤中具有肿瘤抑制功能，并揭示了该发育相关基因的潜在表观遗传调控。
