Knockdown of WWP1 inhibits growth and induces apoptosis in hepatoma carcinoma cells through the activation of caspase3 and p53
Knockdown of WWP1 inhibits growth and induces apoptosis in hepatoma carcinoma cells through the activation of caspase3 and p53
复制标题
敲除 WWP1 通过激活 caspase3 和 p53 抑制肝癌细胞生长并诱导细胞凋亡
DOI：
10.1016/j.bbrc.2014.04.117
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发表时间：
2014-06-06
影响因子：
3.1
通讯作者：
Tong, Tanjun
中科院分区：
文献类型：
--
作者：
Cheng, Qian;Cao, Xiaoxiao;Tong, Tanjun
癌基因的激活和抑癌基因的丢失被认为在人类肝细胞癌（HCC）的发病机制中发挥着关键作用。含有 E3 泛素蛋白连接酶 1 (WWP1) 基因的人类 WW 结构域经常在前列腺癌和乳腺癌中扩增，然而，其在癌症中的作用尚未得到广泛研究。特别是WWP1在HCC中的作用尚未被研究。首先，我们分析了WWP1在HCC样本中的表达。我们发现，与匹配的邻近非肿瘤组织相比，大多数 HCC 癌组织中 WWP1 的蛋白水平较高。此外，WWP1 mRNA 也在所有 7 个 HCC 组织中扩增。使用小干扰RNA敲低内源性WWP1进一步表明WWP1的缺陷抑制细胞生长并导致HCC细胞凋亡。敲低WWP1促进HCC细胞中裂解的caspase3蛋白和p53表达，抑制caspase3可以阻止敲低WWP1诱导的细胞凋亡。总之，这些结果表明，大多数 HCC 组织中 WWP1 的蛋白水平高于非肿瘤组织，并且 WWP1 的敲低通过激活 caspase3 和 p53 抑制 HCC 细胞的生长并诱导细胞凋亡。因此，WWP1基因可能是HCC的潜在分子靶点。 (C) 2014 Elsevier Inc. 保留所有权利。
The activation of oncogenes and the loss of tumor suppressor genes are believed to play critical roles in the pathogenesis of human hepatocellular carcinoma (HCC). The human WW domain containing E3 ubiquitin protein ligase 1 (WWP1) gene is frequently amplified in prostate and breast cancers, however, its role in cancer has not yet been extensively studied. Especially, the role of WWP1 in HCC has not yet been studied. Firstly, we analyzed the expression of WWP1 in HCC samples. We found that protein levels of WWP1 are higher in most HCC cancerous tissues as compared with their matched adjacent non-tumor tissues. Additionally, the WWP1 mRNA was also amplified in all 7 HCC tissues. Knockdown of the endogenous WWP1 using small interfering RNA further showed that deficiency of WWP1 suppressed cell growth and caused apoptosis in HCC cells. Knocking down WWP1 promoted cleaved caspase3 protein and p53 expression in HCC cells, and caspase3 inhibition could prevent cell apoptosis induced by the knockdown of WWP1. All together these results indicate that protein levels of WWP1 in most HCC tissues are higher than non-tumor tissues, and knockdown of WWP1 inhibits growth and induces apoptosis in HCC cells through the activation of caspase3 and p53. Therefore, WWP1 gene might be a potential molecular target of HCC. (C) 2014 Elsevier Inc. All rights reserved.