Lentiviral DDX46 knockdown inhibits growth and induces apoptosis in human colorectal cancer cells
Lentiviral DDX46 knockdown inhibits growth and induces apoptosis in human colorectal cancer cells
复制标题
慢病毒 DDX46 敲低可抑制人结直肠癌细胞的生长并诱导细胞凋亡。
DOI：
10.1016/j.gene.2015.02.020
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发表时间：
2015-04-15
期刊：
影响因子：
3.5
通讯作者：
Cao, Jianping
中科院分区：
文献类型：
--
作者：
Li, Ming;Ma, Yanchao;Cao, Jianping
结直肠癌(CRC)是全球癌症相关死亡的主要原因之一。RNA解旋酶广泛参与多种癌症的发生发展。DDX46属于RNA解旋酶的DEAD BOX家族，参与调节RNA二级结构。DDX46在肿瘤组织中的表达模式以及在结直肠癌进展中的作用尚未确定。在本研究中，我们用免疫组织化学方法检测了DDX46蛋白在人结直肠癌及癌旁组织中的表达。结果显示，87.04%的柱状腺癌组织中DDX46呈高表达，且癌组织中DDX46蛋白的表达明显高于癌旁组织。接下来，用DDX46 RNAi慢病毒(DDX46-RNAi-LV)沉默DDX46在人结肠癌细胞中的表达。经DDX46-RNAi-LV处理的细胞，通过四甲基偶氮唑盐比色法和可见的集落形成实验，细胞增殖明显降低。此外，DDX46沉默通过增加切割的caspase-3和PARP的表达而诱导细胞凋亡。这些结果表明，DDX46对结直肠癌细胞的增殖至关重要，是治疗结直肠癌的潜在靶点。(C)2015爱思唯尔B.V.保留所有权利。
Colorectal cancer (CRC) is one of the leading causes of cancer related deaths worldwide. RNA helicases have been widely implicated in various types of cancer development. DDX46 belongs to the DEAD box family of RNA helicases, which are involved in the regulation of secondary RNA structures. The expression pattern of DDX46 in cancer tissues and the role of DDX46 in CRC progression have not been determined. In this study, we detected DDX46 protein expression in human CRC and adjacent tissues using immunohistochemistry. Our results showed that 87.04% of the columnar adenocarcinoma cases displayed high levels of focal nuclear DDX46 staining, and DDX46 protein expression was strongly increased in CRC tissues compared to adjacent tissues. Next, DDX46 RNAi lentivirus (DDX46-RNAi-LV) was used to silence the expression of DDX46 in the human colon carcinoma cells. Cells treated with the DDX46-RNAi-LV exhibited markedly reduced cell proliferation assessed by the MTT assay and visualized colony formation. Moreover, DDX46 silencing resulted in apoptotic induction via increased expression of cleaved caspase-3 and PARP. These results indicate that DDX46 is critical for CRC cell proliferation and is a potential therapeutic target for CRC treatment. (C) 2015 Elsevier B.V. All rights reserved.