Knockdown of Uba2 inhibits colorectal cancer cell invasion and migration through downregulation of the Wnt/-catenin signaling pathway
Knockdown of Uba2 inhibits colorectal cancer cell invasion and migration through downregulation of the Wnt/-catenin signaling pathway
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DOI：
10.1002/jcb.26890
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发表时间：
2018-08-01
影响因子：
4
通讯作者：
Meng, Xiangwei
中科院分区：
文献类型：
--
作者：
Cheng, Hongjing;Sun, Xun;Meng, Xiangwei
结直肠癌是严重威胁人类健康的疾病，死亡率很高。目前还没有有效的治疗终末期结直肠癌的方法。近年来，分子靶向治疗在肿瘤治疗中受到越来越多的关注。特别是，SUMO激活酶的重要组成部分Uba 2的作用已被强调，它在某些癌症的进展中起着重要作用;然而，它在结直肠癌中的作用仍不清楚。因此，本研究的目的是评估Uba 2与结直肠癌的关系。在两个结直肠癌细胞系中敲除Uba 2表达，并进行基因微阵列分析，然后进行增殖、迁移和侵袭测定。Uba 2基因敲低可影响多个基因的表达，并显著抑制癌细胞的增殖、迁移和侵袭。为了确定潜在的机制，在敲低细胞系中评估相关信号传导途径和分子的表达。Uba 2参与了大肠癌的发生、侵袭和转移，其机制可能是通过调节Wnt信号通路，促进大肠癌细胞的上皮-间质转化行为。因此，Uba 2有望成为大肠癌的重要癌蛋白和潜在的治疗靶点。
Colorectal cancer is a serious threat to human health, and has a high mortality rate. There is currently no effective therapy for end-stage colorectal cancer. In recent years, molecular targeted therapy has received increasing attention for cancer treatment. In particular, the role of Uba2, a vital component of SUMO-activating enzyme, has been highlighted, which plays important roles in the progression of certain cancers; however, its role in colorectal cancer remains unclear. Accordingly, the aim of this study was to evaluate the relationship between Uba2 and colorectal cancer. Uba2 expression was knocked down in two colorectal cancer cell lines, and gene microarray analysis was conducted, followed by proliferation, migration, and invasion assays. Uba2 knockdown influenced the expression of several genes, and significantly inhibited the proliferation, migration, and invasion of cancer cells. To determine the underlying mechanism, the expression of related signaling pathways and molecules was evaluated in the knockdown cell lines. Overall, the results suggest that Uba2 participates in the progression, invasion, and metastasis of colorectal cancer, and the possible mechanism is via regulating the Wnt signaling pathway and enhancing epithelial-mesenchymal transition behaviors of colorectal cancer cells. Therefore, Uba2 is expected to be an important oncoprotein and potential therapeutic target in colorectal cancer.