Nucleostemin Knockdown Sensitizes Hepatocellular Carcinoma Cells to Ultraviolet and Serum Starvation-Induced Apoptosis.
Nucleostemin Knockdown Sensitizes Hepatocellular Carcinoma Cells to Ultraviolet and Serum Starvation-Induced Apoptosis.
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DOI：
10.1371/journal.pone.0141678
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Tong T
中科院分区：
文献类型：
--
作者：
Yuan F;Cheng Q;Li G;Tong T
核干细胞蛋白（NS）是一种GTP结合蛋白，主要在胚胎和成体干细胞中表达，但在终末分化细胞中不表达。NS在维持干细胞和某些类型的癌细胞的持续增殖中起重要作用。然而，NS在肝细胞癌（HCC）中的作用仍不清楚。因此，本研究旨在阐明NS在HCC中的作用。首先，我们证实NS在大多数HCC细胞系和肝癌组织中高表达。通过MTT和细胞增殖试验检测到NS敲低诱导MHCC 97 H细胞活力严重下降。接下来，我们使用紫外线（UV）和血清饥饿诱导的细胞凋亡模型来研究NS抑制或上调是否影响HCC细胞凋亡。经紫外线处理或血清饥饿后，转染NS小干扰RNA的MHCC 97 H和Bel 7402细胞凋亡明显增强，而NS过表达抑制了紫外线和血清诱导的HCC细胞凋亡。此外，在UV照射后，NS的抑制增加了促凋亡蛋白caspase 3的表达，降低了抗凋亡蛋白Bcl-2的表达。caspase 3抑制剂可明显抑制NS敲低诱导的细胞凋亡。总之，我们的研究表明NS在大多数肝癌组织中的过表达与其匹配的周围组织相比，和沉默NS促进UV和血清饥饿诱导的MHCC 97 H和Bel 7402细胞的凋亡。因此，NS基因可能是肝癌治疗的一个潜在靶点。
Nucleostemin (NS) is a GTP-binding protein that is predominantly expressed in embryonic and adult stem cells but not in terminally differentiated cells. NS plays an essential role in maintaining the continuous proliferation of stem cells and some types of cancer cells. However, the role of NS in hepatocellular carcinoma (HCC) remains unclear. Therefore, this study aimed to clarify the role of NS in HCC. First, we demonstrated high expression of NS in most HCC cell lines and liver cancer tissues. NS knockdown induced a severe decline in cell viability of MHCC97H cells as detected by MTT and cell proliferation assays. Next, we used ultraviolet (UV) and serum starvation-induced apoptosis models to investigate whether NS suppression or up-regulation affects HCC cell apoptosis. After UV treatment or serum starvation, apoptosis was strongly enhanced in MHCC97H and Bel7402 cells transfected with small interfering RNA against NS, whereas NS overexpression inhibited UV- and serum-induced apoptosis of HCC cells. Furthermore, after UV irradiation, inhibition of NS increased the expression of pro-apoptosis protein caspase 3 and decreased the expression of anti-apoptosis protein Bcl-2. A caspase 3 inhibitor could obviously prevent NS knockdown-induced apoptosis. In conclusion, our study demonstrated overexpression of NS in most HCC tissues compared with their matched surrounding tissues, and silencing NS promoted UV- and serum starvation-induced apoptosis of MHCC97H and Bel7402 cells. Therefore, the NS gene might be a potential therapeutic target of HCC.