Chmp1A acts as a tumor suppressor gene that inhibits proliferation of renal cell carcinoma
Chmp1A acts as a tumor suppressor gene that inhibits proliferation of renal cell carcinoma
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Chmp1A 作为抑癌基因抑制肾细胞癌的增殖
DOI：
10.1016/j.canlet.2012.01.010
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发表时间：
2012-06-28
期刊：
影响因子：
9.7
通讯作者：
Xuan, Yaoxian
中科院分区：
文献类型：
--
作者：
You, Zhenqiang;Xin, Yanfei;Xuan, Yaoxian
肾细胞癌（RCC）是一种高度恶性且常常致命的肾脏疾病。Chmp 1A是转运所需的内体分选复合物（ESCRT-III）家族的成员，在细胞质中将蛋白质分选到多泡体（MVB）中发挥作用。Chmp 1A是一种抑癌基因，在胰腺癌细胞中有报道。本研究采用实时荧光定量RT-PCR和Western blot检测了人肾细胞癌组织和肾癌细胞中Chmp 1A的表达水平。我们发现，与癌旁组织和正常肾细胞相比，肾细胞癌组织和肾肿瘤细胞中Chmp 1A的表达水平显著降低。此外，通过shRNA抑制Chmp 1A表达可诱导正常肾细胞中的肿瘤形成。然而，抑制Chmp 1A并不显著影响体外肿瘤细胞增殖和体内肿瘤进展。有趣的是，使用真核质粒过表达Chmp 1A抑制体外肾肿瘤细胞的增殖和体内肾肿瘤的生长。因此，我们的研究结果表明，Chmp 1A功能作为一个肿瘤抑制基因在肾细胞，并可能是一个有用的目标，用于治疗肾细胞癌。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
Renal cell carcinoma (RCC) is a highly malignant and often fatal disease of the kidney. Chmp1A is a member of the Endosomal Sorting Complex Required for Transport (ESCRT-III) family, and plays a role in the cytoplasm in sorting proteins to the multivesicular body (MVB). Chmp1A functions as a tumor suppressor gene and has been reported in pancreatic tumor cells. Here, we examined the expression level of Chmp1A in human RCC tissues and renal tumor cells by real-time quantitative RT-PCR and western blot. We found that the expression level of Chmp1A is significantly lower in RCC tissues and renal tumor cells compared with adjacent non-tumorous tissues and normal renal cells. Additionally, inhibition of Chmp1A expression by shRNA induced tumor formation in normal renal cells. However, inhibition of Chmp1A did not significantly affect tumor cell proliferation in vitro and tumor progression in vivo. Interestingly, overexpression of Chmp1A using a eukaryotic plasmid inhibited the proliferation of renal tumor cells in vitro and the growth of renal tumor in vivo. Thus, our results demonstrate that Chmp1A functions as a tumor suppressor gene in renal cells and may be a useful target for treatment of RCC. (C) 2012 Elsevier Ireland Ltd. All rights reserved.