Department of Anatomy and Neurobiology, Virginia Commonwealth University, Norfolk, VA, USA.
J Neurosurg. 2012 Apr;116(4):843-53. doi: 10.3171/2011.11.JNS111455. Epub 2012 Feb 7.
The Wilms tumor 1 (WT1) protein-a developmentally regulated transcription factor-is aberrantly expressed in gliomas and promotes their malignant phenotype. However, little is known about the molecular allies that help it mediate its oncogenic functions in glioma cells.
The authors used short interfering RNA (siRNA) to suppress WT1 expression in glioblastoma (GBM) cells and evaluated the effect of this on GBM cell invasiveness. Gene expression analysis was then used to identify the candidate genes that were altered as a result of WT1 silencing. One candidate target, CD97, was then selected for further investigation into its role by suppressing its expression using siRNA silencing, followed by proliferation and invasion assays.
WT1 levels were reliably and reproducibly suppressed by siRNA application. This resulted in a significant decrease in cellular invasiveness. Microarray analyses identified the gene products that were consistently downregulated (27) and upregulated (11) with WT1 silencing. Of these, CD97 expression was consistently suppressed across the 3 different GBM cell lines studied and was found on further investigation to significantly impact GBM cell invasiveness.
Although CD97 expression in gliomas has not been described previously, we conclude that the possible upregulation of CD97 mediated by WT1 promotes cellular invasiveness-one of the most characteristic and challenging aspects of glial tumor cells. Further studies are needed to clarify the nature of this regulation and its impact, as CD97 could represent a novel target for antiglioma therapies.
Wilms 肿瘤 1 （WT1）蛋白——一种发育调节转录因子——在神经胶质瘤中异常表达，并促进其恶性表型。然而，人们对帮助其在神经胶质瘤细胞中介导致癌功能的分子盟友知之甚少。
作者使用短发夹 RNA （siRNA）抑制神经胶质瘤（GBM）细胞中的 WT1 表达，并评估其对 GBM 细胞侵袭性的影响。然后，使用基因表达分析来鉴定由于 WT1 沉默而改变的候选基因。然后，选择一个候选靶标 CD97，通过使用 siRNA 沉默抑制其表达，进一步研究其在增殖和侵袭测定中的作用。
WT1 水平通过 siRNA 应用可靠且可重复地抑制。这导致细胞侵袭性显著降低。微阵列分析确定了与 WT1 沉默一致下调（27）和上调（11）的基因产物。在这其中，CD97 的表达在 3 种不同的 GBM 细胞系中均受到一致抑制，并在进一步研究中发现其显著影响 GBM 细胞的侵袭性。
尽管先前尚未描述 CD97 在神经胶质瘤中的表达，但我们得出结论，WT1 介导的 CD97 可能上调促进了细胞侵袭性——这是神经胶质肿瘤细胞最具特征性和挑战性的方面之一。需要进一步研究来阐明这种调节及其影响的性质，因为 CD97 可能代表新的抗神经胶质瘤治疗靶点。
