Reduced expression of Slit2 in renal cell carcinoma
Reduced expression of Slit2 in renal cell carcinoma
复制标题
肾细胞癌中 Slit2 表达降低
DOI：
10.1007/s12032-013-0768-4
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发表时间：
2014-01-01
期刊：
影响因子：
3.4
通讯作者：
Zhang, Jun
中科院分区：
文献类型：
--
作者：
Ma, Wei-Jie;Zhou, Yu;Zhang, Jun
Slit2最初被认为是神经系统中重要的轴突导向分子，被认为参与多种细胞过程。最近，Slit2被报道在多种肿瘤中作为潜在的肿瘤抑制因子发挥作用。本研究系统分析了Slit 2在肾癌组织中的表达水平。与癌旁正常肾组织相比，肾细胞癌组织中Slit2 mRNA和蛋白表达均显著下调。甲基化特异性PCR检测结果显示，两种肾癌细胞系中Slit2基因启动子均发生甲基化。药理学去甲基化在Slit2弱表达的癌细胞系中显著诱导Slit2表达。此外，亚硫酸氢盐基因组测序证实Slit2启动子存在密集甲基化。此外，在配对的RCC样品中，在38名患者中的8名（21.1%）中观察到Slit 2甲基化，这与RCC中Slit 2的下调密切相关。因此，Slit2也可能是肾细胞癌中潜在的肿瘤抑制因子，其在肾细胞癌中下调部分归因于启动子甲基化。
Slit2, initially identified as an important axon guidance molecule in the nervous system, was suggested to be involved in multiple cellular processes. Recently, Slit2 was reported to function as a potential tumor suppressor in diverse tumors. In this study, we systematically analyzed the expression level of Slit2 in renal cell carcinoma. Compared to paired adjacent non-malignant tissues, both Slit2 mRNA and protein expression were significantly down-regulated in renal cell carcinoma (RCC). Methylation-specific PCR showed that Slit2 promoter was methylated in two renal carcinoma cell lines. Pharmacologic demethylation dramatically induced Slit2 expression in cancer cell lines with weak expression of Slit2. Besides, bisulfite genomic sequencing confirmed that dense methylation existed in Slit2 promoter. Furthermore, in paired RCC samples, Slit2 methylation was observed in 8 out of 38 patients (21.1 %), which was well correlated with the down-regulation of Slit2 in RCC. Therefore, Slit2 may also be a potential tumor suppressor in RCC, which is down-regulated in RCC partially due to promoter methylation.