The oncogenic role of Wnt10a in colorectal cancer through activation of canonical Wnt/β-catenin signaling
The oncogenic role of Wnt10a in colorectal cancer through activation of canonical Wnt/β-catenin signaling
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DOI：
10.3892/ol.2019.10035
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发表时间：
2019-04-01
期刊：
影响因子：
2.9
通讯作者：
Zhang, Yongchen
中科院分区：
文献类型：
--
作者：
Li, Jinlong;Zhang, Zhaoli;Zhang, Yongchen
结直肠癌是世界范围内癌症相关死亡的主要原因之一。WNT家族成员10A(Wnt10a)是一种与肾癌发生发展相关的癌基因，在结直肠癌细胞系SW480中高表达。然而，Wnt10a在结直肠癌中的作用却鲜有报道。在本研究中，RT-qPCR方法检测到40例肿瘤组织中Wnt10a的表达水平高于配对的对照组织。临床病理关联分析显示，WNT10a的表达与肿瘤分期有关(T3+T4，P=0.015)。此外，WNT10a在SW480、SW620和HCT116细胞中高表达。为探讨Wnt10a在结直肠癌中的作用，采用siRNA技术下调Wnt10a在HCT116细胞中的表达。Wnt10a基因敲除后，CCK-8检测细胞增殖明显受抑55%，Transwell检测细胞迁移率下降50%。此外，Western印迹分析表明，Wnt10a基因敲除后，β-连环素、细胞周期蛋白D1、淋巴增强因子1和蛋白激酶B的表达水平降低，这与Wnt/β-连环素特异性抑制剂LGK-974的结果一致。因此，我们认为Wnt10a下调激活了HCT116细胞中的Wnt/β-catenin信号通路。综上所述，本研究表明Wnt10a可能通过激活Wnt/β-catenin信号通路在结直肠癌的发生发展过程中发挥致癌作用。
Colorectal cancer (CRC) is one of the major causes of cancer-associated mortality worldwide. Wnt family member 10A (Wnt10a) is an oncogene associated with the carcinogenesis and progression of renal cell carcinoma, and is strongly expressed in the CRC cell line SW480. However, the role of Wnt10a in CRC has been rarely reported. In the present study, the expression levels of Wnt10a were higher in 40 tumor tissues compared with in paired control tissues, as determined by RT-qPCR method. In addition, the clinic opathological association analysis indicated that Wnt10a expression was associated with tumor stage (T3+T4, P=0.015). Furthermore, Wnt10a was highly expressed in the SW480, SW620 and HCT116 cell lines. In order to explore the role of Wnt10a in CRC, Wnt10a expression was knocked down by siRNA technology in HCT116 cell line. Cell proliferation was significantly inhibited by 55% in CCK-8 assay following Wnt10a knockdown and cell migration rate was decreased by 50% in Transwell assay. In addition, western blot analysis demonstrated that Wnt10a knockdown decreased the expression levels of beta-catenin, cyclin D1, lymphoid enhancer-binding factor 1 and protein kinase B, which was consistent with results obtained with the Wnt/beta-catenin specific inhibitor LGK-974. It was thus suggested that Wnt10a downregulation inactivated the Wnt/beta-catenin signaling pathway in HCT116 cells. In conclusion, the present study demonstrated that Wnt10a may have an oncogenic role during carcinogenesis of CRC through activation of Wnt/beta-catenin signaling.