LncRNA ADPGK-AS1 promotes pancreatic cancer progression through activating ZEB1 -mediated epithelial–mesenchymal transition

作者：Suzhen Song, Weihua Yu, Sen Lin, Mingbao Zhang, Teng Wang, Shuang Guo, Hongbo Wang · 发表于：Cancer Biology & Therapy · 年份：2018 · DOI：10.1080/15384047.2018.1423912 · 被引用次数：38 · 研究领域：Cancer-related molecular mechanisms research、MicroRNA in disease regulation、Circular RNAs in diseases

OBJECTIVE: This study was conducted to investigate the effects of ADP dependent glucokinase antisense RNA 1 (ADPGK-AS1)/ miR-205-5p/ zinc finger E-box binding homeobox 1 (ZEB1) on PC cells. METHODS: Differentially expressed lncRNAs and miRNAs in pancreatic cancer (PC) were identified by microarray analysis. In silico ceRNA analysis was conducted to find out the interactions among lncRNAs, miRNAs and mRNAs. Quantitative real-time PCR (qRT-PCR) was utilized to examine the expression of miR-205-5p and lncRNA ADPGK-AS1 in PC and non-cancerous cells. The association between miR-205-5p and ADPGK-AS1 as well as miR-205-5p and ZEB1 was determined by dual-luciferase reporter gene assay. After manipulating the expression of ADPGK-AS1, mir-205-5p and ZEB1 in PANC-1 and SW-1990 cells, cell proliferation, migration, invasion and apoptosis were respectively confirmed by cell counting kit-8 (CCK-8) assay, transwell assay and TUNEL. Western blot was applied to examine the expression of Epithelial-mesenchymal Transition-related proteins. In vivo experiment was conducted to further determine the effect of miR-205-5p/ZEB1 on tumorigenic ability of PC cells. RESULTS: MiR-205-5p was low-expressed while ZEB1 and ADPGK-AS1 were high-expressed in PC tissues and cells compared with the normal. Dual-luciferase reporter gene assay proved that ADPGK-AS1 could directly target miR-205-5p and miR-205-5p could directly target ZEB1 3'UTR. The expression of MiR-205-5p was negatively correlated with proliferat...