CDH17 is a downstream effector of HOXA13 in modulating the Wnt/β-catenin signaling pathway in gastric cancer

摘要

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.