Overexpression of long non-coding RNA-CTD903 inhibits colorectal cancer invasion and migration by repressing Wnt/β-catenin signaling and predicts favorable prognosis
Overexpression of long non-coding RNA-CTD903 inhibits colorectal cancer invasion and migration by repressing Wnt/β-catenin signaling and predicts favorable prognosis
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长链非编码 RNA-CTD903 的过表达通过抑制 Wnt/β-catenin 信号传导抑制结直肠癌侵袭和迁移，并预测良好的预后
DOI：
10.3892/ijo.2016.3447
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发表时间：
2016-06-01
影响因子：
5.2
通讯作者：
Wang, Lei
中科院分区：
文献类型：
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作者：
Yuan, Zixu;Yu, Xihu;Wang, Lei
越来越多的证据表明，长链非编码RNA（lncRNA）在肿瘤的发生、发展中起着重要作用，但其在转移性结直肠癌（CRC）中的作用及机制尚不清楚。本研究旨在检测lncRNA-CTD 903在CRC患者中的表达水平和预后作用，该基因是根据一个微阵列数据选择的。研究了在CRC细胞系中沉默或过表达CTD 903后对细胞侵袭、迁移和增殖的影响。同时观察了EMT（上皮-间充质转化）现象及其对细胞粘附的影响。通过蛋白质印迹法确定CTD 903与EMT标志物如E-cadherin、N-cadherin、β-catenin、ZEB 1、ZO-1、Snail和Twist之间的关联。我们的研究结果显示，lncRNA-CTD 903在115例CRC患者中的表达强烈上调，与邻近正常组织相比。多因素考克斯比例风险模型分析显示CTD 903是结直肠癌患者预后良好的独立预测因素。在RKO和SW 480中敲低CTD 903后，细胞侵袭和迁移均增加，并且细胞表现出EMT样外观，沿着粘附能力降低。此外，在DLD 1和HCT 116中过表达CTD 903逆转了这些表型。此外，下调CTD 903增强了Wnt/β-连环蛋白的激活，随后增加了转录因子（Twist和Snail）的表达，沿着间充质标志物波形蛋白的增加和上皮标志物ZO-1水平的降低，而过表达的CTD 903证实了这些关联。总之，本研究表明LncRNA-CTD 903在CRC中作为肿瘤抑制剂，可以通过抑制Wnt/β-catenin信号传导来抑制细胞侵袭和迁移，这在EMT和CRC转移中起重要作用。
Accumulating evidence reveals that long non-coding RNA (lncRNA) is essential for tumorigenesis and progression, but little is known about its roles and mechanisms in metastatic colorectal cancer (CRC). This study aimed to detect expression level and prognostic role of lncRNA-CTD903 in CRC patients, which was selected based on one microarray data. The effects on cell invasion, migration and proliferation were investigated after silencing or overexpression of CTD903 in CRC cell lines. We also observed the EMT (epithelial-mesenchymal transition) phenomenon and effect on cell adhesion. The associations between CTD903 and EMT markers, such as E-cadherin, N-cadherin, beta-catenin, ZEB1, ZO-1, Snail, and Twist, were determined by western blotting. Our results showed lncRNA-CTD903 expression was strongly upregulated in 115 CRC patients, comparing to adjacent normal tissues. CTD903 was proven to be an independent predicted factor of favorable prognosis in CRC patients by using multivariate Cox proportional hazards model. After knockdown of CTD903 in RKO and SW480, both cell invasion and migration increased, and cells exhibited EMT-like appearance, along with reduced adhering ability. Moreover, overexpression of CTD903 in DLD1 and HCT116 reversed these phenotypes. Furthermore, downregulation of CTD903 enhanced Wnt/beta-catenin activation and subsequently increased transcription factors (Twist and Snail) expression, along with increased mesenchymal marker Vimentin and decreased epithelial marker ZO-1 level, while overexpressed CTD903 confirmed these associations. In conclusion, this study shows that LncRNA-CTD903 acts as a tumor suppressor in CRC and can inhibit cell invasion and migration through repressing Wnt/beta-catenin signaling, which plays important roles in EMT and CRC metastasis.