Survivin-targeting Artificial MicroRNAs Mediated by Adenovirus Suppress Tumor Activity in Cancer Cells and Xenograft Models.
Survivin-targeting Artificial MicroRNAs Mediated by Adenovirus Suppress Tumor Activity in Cancer Cells and Xenograft Models.
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腺病毒介导的靶向生存素的人工 MicroRNA 可抑制癌细胞和异种移植模型中的肿瘤活性
DOI：
10.1038/mtna.2014.59
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发表时间：
2014-11-04
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
生存素在大多数人类肿瘤和胎儿组织中高表达，而在终末分化细胞中不表达。它通过负向调节细胞凋亡和促进细胞分裂来促进肿瘤细胞增殖。生存素的选择性表达模式表明它可能是癌症治疗的合适靶点，它会促进转化细胞的死亡，但不会促进正常细胞的死亡。这是使用针对生存素的人工 microRNA (amiRNA) 进行测试的。经过筛选，两个有效的 amiRNA 被鉴定出来，它们可以降低生存素的表达，并将其克隆到复制缺陷型腺病毒载体中。感染重组载体的肿瘤细胞下调生存素表达并发生细胞凋亡。进一步的研究表明，细胞凋亡与 caspase 3 和裂解聚 (ADP-核糖) 聚合酶的增加以及 p53 信号通路的激活有关。此外，amiRNA 治疗导致有丝分裂受阻，细胞周期停滞在 G2/M 期。在体内，腺病毒载体表达的靶向生存素的 amiRNA 有效延迟了小鼠异种移植模型中肝细胞癌和宫颈癌的生长。这些结果表明，amiRNA 沉默存活蛋白具有治疗癌症的潜力。
Survivin is highly expressed in most human tumors and fetal tissue, and absent in terminally differentiated cells. It promotes tumor cell proliferation by negatively regulating cell apoptosis and facilitating cell division. Survivin's selective expression pattern suggests that it might be a suitable target for cancer therapy, which would promote death of transformed but not normal cells. This was tested using artificial microRNAs (amiRNAs) targeting survivin. After screening, two effective amiRNAs, which knocked down survivin expression, were identified and cloned into a replication-defective adenoviral vector. Tumor cells infected with the recombinant vector downregulated expression of survivin and underwent apoptotic cell death. Further studies showed that apoptosis was associated with increases in caspase 3 and cleaved Poly (ADP-ribose) polymerase, and activation of the p53 signaling pathway. Furthermore, amiRNA treatment caused blockade of mitosis and cell cycle arrest at the G2/M phase.In vivo, survivin-targeting amiRNAs expressed by adenoviral vectors effectively delayed growth of hepatocellular and cervical carcinomas in mouse xenograft models. These results indicate that silencing of survivin by amiRNA has potential for treatment of cancer.
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影响因子：
11.2
作者：
Bader AG;Brown D;Winkler M
通讯作者：
Winkler M
影响因子：
5.4
作者：
BETT, AJ;PREVEC, L;GRAHAM, FL
通讯作者：
GRAHAM, FL
影响因子：
2.5
作者：
Baek, Mi Na;Jung, Kyoung Hwa;Chai, Young Gyu
通讯作者：
Chai, Young Gyu
影响因子：
5.7
作者：
Carrasco, Rosa A.;Stamm, Nancy B.;Patel, Bharvin K. R.
通讯作者：
Patel, Bharvin K. R.
DOI：
10.1016/j.bbrc.2006.09.143
发表时间：
2006-12-01
影响因子：
3.1
作者：
Kim, Ji Young;Chung, Jin-Yong;Kim, Jong-Min
通讯作者：
Kim, Jong-Min