siRNA targeting LMP1-induced apoptosis in EBV-positive lymphoma cells is associated with inhibition of telornerase activity and expression
siRNA targeting LMP1-induced apoptosis in EBV-positive lymphoma cells is associated with inhibition of telornerase activity and expression
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DOI：
10.1016/j.canlet.2005.02.010
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发表时间：
2006-02-08
期刊：
影响因子：
9.7
通讯作者：
Zeng, YX
中科院分区：
文献类型：
--
作者：
Mei, YP;Zhu, XF;Zeng, YX
EB病毒（EBV）与B细胞恶性肿瘤密切相关。然而，EBV是否是淋巴瘤细胞增殖和存活所必需的仍然是未知的。本研究应用靶向LMP 1的小干扰RNA（siRNA）研究LMP 1对EBV阳性淋巴母细胞样B细胞系增殖的影响。构建了稳定编码21-nt小RNA的质粒，该质粒特异性地、有效地干扰LMP 1，导致LMP 1 mRNA的大量丢失和LMP 1蛋白表达的显著降低。我们的数据表明，在淋巴母细胞样B细胞系中，LMP 1基因敲低后，细胞增殖被完全抑制，并诱导凋亡。此外，我们发现，抑制LMP 1导致端粒酶蛋白表达下调，降低端粒酶活性在淋巴瘤细胞。在EBV阴性的鼻咽癌细胞系中，转染表达LMP 1的质粒可显著增强端粒酶蛋白的表达。我们的结果表明，siRNA靶向LMP 1可以诱导EBV阳性淋巴瘤细胞凋亡，并与端粒酶活性和表达的抑制有关。siRNA介导的LMP 1沉默可能对预防和治疗EBV相关肿瘤具有治疗价值。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
Epstein-BaIT Virus (EBV) is closely associated with B cell malignancies. However, whether EBV appears to be absolutely required for cell proliferation and survival in lymphoma cells is still unknown. In this Study, small interfering RNA (siRNA) targeting LMP1 was employed to investigate the effect of LMP1 on cell proliferation in EBV-positive lymphoblastoid B-cell line. A plasmid stable encoding 21-nt small RNA specifically and efficiently interfering LMP1 was constructed, resulting in a Substantial loss of LMP1 mRNA and a significantly decreased LMP1 protein expression. Our data demonstrated that cell proliferation was completely inhibited and apoptosis was induced after knockdown of LMP1 gene in lymphoblastoid B-cell line. Also, we found that suppression of LMP1 caused downregulation of telomerase protein expression and decreased telomerase activity in lymphoma cells. In EBV-negative NPC cell line, transfection of plasmid expressing LMP1 greatly enhanced telomerase protein expression. Our results Suggested that siRNA targeting LMP1 can induce apoptosis in EBV-Positive lymphoma cells and is associated with inhibition of telomerase activity and expression. siRNA-directed LMP1 silencing may be of the therapeutic value for preventing and treating those EBV-associated tumors. (c) 2005 Elsevier Ireland Ltd. All rights reserved.