Silencing of ROR1 and FMOD with siRNA results in apoptosis of CLL cells
Silencing of ROR1 and FMOD with siRNA results in apoptosis of CLL cells
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DOI：
10.1111/j.1365-2141.2010.08362.x
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发表时间：
2010-11-01
影响因子：
6.5
通讯作者：
Mellstedt, Hakan
中科院分区：
文献类型：
--
作者：
Choudhury, Aniruddha;Derkow, Katja;Mellstedt, Hakan
我们以前已经证明ROR 1和FMOD（纤维调节蛋白）是两个基因上调慢性淋巴细胞白血病（CLL）细胞相比，正常的血液B细胞。在这项研究中，siRNA被用于特异性沉默CLL细胞、健康B细胞和人成纤维细胞系中的ROR 1和FMOD表达。siRNA处理诱导FMOD和ROR 1 mRNA的特异性减少（75-95%）。FMOD和ROR 1特异性抗体的Western印迹分析表明，siRNA处理后48 h，蛋白质显著下调。FMOD和ROR 1的沉默导致CLL细胞的统计学显著（P < 0.05-0.001）凋亡，但不导致来自正常供体的B细胞的凋亡。用FMOD和ROR 1 siRNA处理的人成纤维细胞系没有发生凋亡。这是第一份证明ROR 1和FMOD可能参与CLL细胞存活的报告。特别是ROR 1被进一步探索为CLL治疗的潜在靶标。
P>We have previously demonstrated that ROR1 and FMOD (fibromodulin) are two genes upregulated in chronic lymphocytic leukaemia (CLL) cells compared to normal blood B cells. In this study, siRNAs were used to specifically silence ROR1 and FMOD expression in CLL cells, healthy B cells and human fibroblast cell lines. siRNA treatment induced a specific reduction (75-95%) in FMOD and ROR1 mRNA. Western blot analysis with specific antibodies for FMOD and ROR1 demonstrated that the proteins were significantly downregulated 48 h after siRNA treatment. Silencing of FMOD and ROR1 resulted in statistically significant (P < 0.05-0.001) apoptosis of CLL cells but not of B cells from normal donors. Human fibroblast cell lines treated with FMOD and ROR1 siRNA did not undergo apoptosis. This is the first report demonstrating that ROR1 and FMOD may be involved in the survival of CLL cells. ROR1 in particular is further explored as potential target for therapy in CLL.