Silencing glypican-3 expression induces apoptosis in human hepatocellular carcinoma cells
Silencing glypican-3 expression induces apoptosis in human hepatocellular carcinoma cells
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DOI：
10.1016/j.bbrc.2012.02.069
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发表时间：
2012-03-23
影响因子：
3.1
通讯作者：
Zeng, Xiangting
中科院分区：
文献类型：
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作者：
Liu, Shiyuan;Li, Yumin;Zeng, Xiangting
肝细胞癌（Hepatocellular carcinoma，HCC）是最常见的内脏恶性肿瘤之一。磷脂酰肌醇蛋白聚糖-3（GPC 3）参与了肝癌发生的生物学和分子生物学过程。我们使用RNA干扰来评估GPC 3抑制在翻译水平上的分子效应，并首次证明GPC 3沉默导致Bax/Bcl-2比率的显著升高、细胞色素c从线粒体的释放和caspase-3的激活。结果表明，GPC 3通过Bax/Bcl-2/细胞色素c/caspase-3信号通路的功能障碍，增强细胞对凋亡的抵抗，从而调节细胞增殖，在肝癌的发生中起重要作用。因此，GPC 3的敲除将成为肝癌靶向基因治疗的一种新方法，值得进一步研究。(C)2012 Elsevier Inc. All rights reserved.
Hepatocellular carcinoma (HCC) is one of the most common internal malignant tumors. Glypican-3 (GPC3) is involved in the biological and molecular events in the tumorigenesis of HCC. We used RNA interference to evaluate the molecular effects of GPC3 suppression at the translational level and demonstrated for the first time that GPC3 silencing results in a significant elevation of the Bax/Bcl-2 ratio, the release of cytochrome c from mitochondria and the activation of caspase-3. The results suggest that GPC3 regulates cell proliferation by enhancing the resistance to apoptosis through the dysfunction of the Bax/Bcl-2/cytochrome c/caspase-3 signaling pathway and therefore plays a critical role in the tumorigenesis of HCC. Thus, the knockdown of GPC3 should be further investigated as an attractive novel approach for the targeted gene therapy of HCC. (C) 2012 Elsevier Inc. All rights reserved.