CDH17 is a downstream effector of HOXA13 in modulating the Wnt/β-catenin signaling pathway in gastric cancer.
CDH17 is a downstream effector of HOXA13 in modulating the Wnt/β-catenin signaling pathway in gastric cancer.
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DOI：
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发表时间：
2017-03
影响因子：
3.3
通讯作者：
Lizhen Qu;Yi Zhong;Z. Zheng;Ruixi Zhao
中科院分区：
文献类型：
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作者：
Lizhen Qu;Yi Zhong;Z. Zheng;Ruixi Zhao
目的探讨HOXA13和CDH17在胃癌中共同上调的机制、HOXA13和CDH17参与的信号转导途径及其在胃癌细胞中的作用。材料与方法检索ArrayExpress中研究胃癌组织中异常表达基因的相关芯片。利用cBioPortal和UCSC Xena分析HOXA13和CDH17在TCGA数据库中的共表达情况。用双荧光素酶法检测HOXA13对CDH17表达的调节作用。Western blotting检测HOXA13和CDH17在Wnt/β-catenin信号通路中的作用。通过CCK-8细胞生长实验、Transwell细胞侵袭实验和caspase-3活性的流式细胞术检测HOXA13和CDH17在胃癌细胞中的作用。结果HOXA13和CDH17在胃癌组织中表达上调，且高度相关。HOXA13过表达显著增加CDH17mRNA和蛋白的表达，并显著增强整合了HOXA13结合位点的荧光素酶报告基因的转录活性。HOXA13 shRNA和CDH17 shRNA对β-连环蛋白表达的抑制作用相似，而shCDH17抑制HOXA13诱导的β-连环蛋白表达上调。HOXA13shRNA和CDH17shRNA抑制SGC-7901细胞的增殖和侵袭，增加细胞凋亡。结论HOXA13可通过与其启动子结合而上调CDH17的转录。CDH17是HOXA13调控胃癌细胞Wnt/β-catenin信号通路的下游效应分子。HOXA13shRNA和CDH17shRNA均能抑制胃癌细胞的增殖和侵袭，增加其凋亡率。
OBJECTIVE In this study, we investigated the mechanism underlying co-upregulation of HOXA13 and CDH17 in gastric cancer, the signaling pathway in which HOXA13 and CDH17 involve in and their functional role in gastric cancer cells. MATERIALS AND METHODS Relevant microarrays investigated the dysregulated genes in gastric cancer tissues were searched in ArrayExpress. The co-expression of HOXA13 and CDH17 was analyzed in the gastric cancer patient cohort in TCGA database using cBioportal and UCSC Xena. The regulative effect of HOXA13 on CDH17 expression was examined by dual luciferase assay. The involvement of HOXA13 and CDH17 in the Wnt/beta-catenin signaling pathway was assessed by Western blotting. The functional role of HOXA13 and CDH17 in gastric cancer cells were studied by CCK-8 assay of cell growth, Transwell assay of cell invasion and flow cytometry of active caspase-3. RESULTS HOXA13 and CDH17 expression are upregulated and are highly correlated in gastric cancer tissues. HOXA13 overexpression significantly increased CDH17 mRNA and protein expression and also significantly increased the transcription activity of the luciferase reporter with integrate HOXA13 binding sites. HOXA13 shRNA and CDH17 shRNA had similar effect on reducing the expression of beta-catenin, while shCDH17 abrogated HOXA13 induced upregulation of beta-catenin. HOXA13 shRNA and CDH17 shRNA decreased cell proliferation and invasion and increased cell apoptosis in SGC-7901 cells. CONCLUSIONS HOXA13 can elevate CDH17 transcription via binding to its promoter. CDH17 is a downstream effector of HOXA13 in modulating the Wnt/beta-catenin signaling pathway in gastric cancer cells. Both HOXA13 shRNA and CDH17 shRNA can decrease gastric cancer cell proliferation and invasion and increase their apoptosis.