期刊
ONCOTARGETS AND THERAPY
卷 12, 期 -, 页码 657-667出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/OTT.S175521
关键词
gastric cancer; ZEB2-AS1; miR-143-5p; HIF-1 alpha; cell proliferation; metastasis
资金
- Scientific Research Program of Shaanxi Education Department [12JK0704]
Background: Growing evidence has implicated the important role of the long non-coding RNAs (lncRNAs) in gastric cancer progression. In this study, we examined the expression of lncRNA zinc finger E-box-binding homeobox 2 antisense RNA 1 (ZEB2-AS1) in gastric cancer tissues and elucidated the molecular mechanisms underlying ZEB2-AS1-mediated gastric cancer progression. Methods: Quantitative real-time PCR measured the gene expression level; CCK-8, colony formation and cell invasion assays determined gastric cancer cell proliferation, growth and invasion, respectively; the xenograft nude mice model was used to determine in vivo tumor growth; Bioinformatics analysis and luciferase reporter assay determined the downstream targets of ZEB2-AS1 and miR-143-5p. The expression of ZEB2-AS1 was upregulated in gastric cancer cell lines. Results: Knockdown of ZEB2-AS1 suppressed gastric cancer cell proliferation, growth and invasion, and also suppressed in vivo tumor growth in the nude mice. Overexpression of ZEB2-AS1 potentiated gastric cancer cell proliferation, growth and invasion. Bioinformatics analysis and luciferase reporter assay showed that miR-143-5p was a direct target of ZEB2-AS1 and was negatively regulated by ZEB2-AS1. Furthermore, hypoxia-inducible factor-1 alpha (HIF-1 alpha) was found to be a target of miR-143-5p and was negatively regulated by miR-143-5p. The rescue in vitro assays showed that the effects of ZEB2-AS1 overexpression on gastric cancer cell proliferation, growth and invasion was mediated via miR-143-5p/HIF-1 alpha. ZEB2-AS1 and HIF-1 alpha was upregulated in gastric cancer tissues, while miR-143-5p was down-regulated; and ZEB2-AS1 expression level was inversely correlated with miR-143-5p expression level, and positively correlated with HIF-1 alpha mRNA expression level; while miR-143-5p expression level was inversely correlated with HIF-1 alpha expression level. High ZEB2-AS1 expression level was correlated with poor differentiation, lymph node metastasis and distant metastasis. Conclusion: Collectively, our results indicated that ZEB2-AS1 was up-regulated in gastric cancer tissues and cells and promoted cell proliferation and metastasis through miR-143-5p/HIF-1 alpha pathway, which may provide a promising target for treatment of gastric cancer.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据