Knockdown of DIXDC1 Inhibits the Proliferation and Migration of Human Glioma Cells
Knockdown of DIXDC1 Inhibits the Proliferation and Migration of Human Glioma Cells
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DOI：
10.1007/s10571-016-0433-5
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发表时间：
2017-08-01
影响因子：
4
通讯作者：
Huang, Qingfeng
中科院分区：
文献类型：
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作者：
Chen, Jianguo;Shen, Chaoyan;Huang, Qingfeng
DIX结构域含有1 (DIXDC1)，是人类coiled-coil-DIX1 （Ccd1）的同源物，是Wnt信号通路的正调控因子。最近，它被发现是结肠癌、非小细胞肺癌和胃癌的候选致癌基因。本研究旨在探讨DIXDC1在人胶质瘤中表达的临床意义及其在胶质瘤细胞中的生物学功能。Western blot和免疫组化分析显示DIXDC1在胶质瘤组织和胶质瘤细胞系中过表达。DIXDC1的表达水平与胶质瘤病理分级及Ki-67的表达有明显的相关性。Kaplan-Meier曲线显示，DIXDC1的高表达可能导致胶质瘤患者预后不良。血清饥饿和再饲喂实验表明，DIXDC1的表达与细胞周期有关。为了确定DIXDC1是否能调节胶质瘤细胞的增殖和迁移，我们用靶向DIXDC1的干扰rna转染胶质瘤细胞；使用细胞计数试剂盒(CCK)-8、流式细胞术和集落形成分析研究细胞增殖；并用伤口愈合试验和transwell试验研究细胞迁移。根据我们的数据，敲低DIXDC1可显著抑制胶质瘤细胞的增殖和迁移。这些数据提示DIXDC1可能参与胶质瘤的发展，提示DIXDC1可能成为胶质瘤的潜在治疗策略。
DIX domain containing 1 (DIXDC1), the human homolog of coiled-coil-DIX1 (Ccd1), is a positive regulator of Wnt signaling pathway. Recently, it was found to act as a candidate oncogene in colon cancer, non-small-cell lung cancer, and gastric cancer. In this study, we aimed to investigate the clinical significance of DIXDC1 expression in human glioma and its biological function in glioma cells. Western blot and immunohistochemistry analysis showed that DIXDC1 was overexpressed in glioma tissues and glioma cell lines. The expression level of DIXDC1 was evidently linked to glioma pathological grade and Ki-67 expression. Kaplan-Meier curve showed that high expression of DIXDC1 may lead to poor outcome of glioma patients. Serum starvation and refeeding assay indicated that the expression of DIXDC1 was associated with cell cycle. To determine whether DIXDC1 could regulate the proliferation and migration of glioma cells, we transfected glioma cells with interfering RNA-targeting DIXDC1; investigated cell proliferation with Cell Counting Kit (CCK)-8, flow cytometry assays, and colony formation analyses; and investigated cell migration with wound healing assays and transwell assays. According to our data, knockdown of DIXDC1 significantly inhibited proliferation and migration of glioma cells. These data implied that DIXDC1 might participate in the development of glioma, suggesting that DIXDC1 can become a potential therapeutic strategy for glioma.