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Circular RNA ATXN7 promotes the development of gastric cancer through sponging miR-4319 and regulating ENTPD4.
环状 RNA ATXN7 通过海绵 miR-4319 和调节 entpd4 促进胃癌的发展。
- 影响因子：3.81
- DOI：10.1186/s12935-020-1106-5
- 作者列表："Zhang Z","Wu H","Chen Z","Li G","Liu B
- 发表时间：2020-01-23
Abstract
Background:Circular RNAs (circRNAs) which are shown as a class of RNAs exhibit the importance in the regulation of gene expression and the development of biological process. However, the expression profile and molecular mechanism of circRNA ATXN7 (circATXN7) is still mostly uncertain in gastric cancer (GC). Methods:qRT-PCR analysis was performed to detect the expression of circATXN7, miR-4319 and ENTPD4 in GC tissues and cells. CCK-8, colony formation, EdU, flow cytometry, TUNEL and transwell assays were conducted to assess the effect of circATXN7 or miR-4319 on cell proliferation, apoptosis and invasion. In vivo assays were utilized to further analyze the function of circATXN7 on the tumorigenesis and progression of GC. The interaction between miR-4319 and circATXN7 (or ENTPD4) was verified using luciferase reporter and RNA pull-down assays. Results:The results showed an upregulated circATXN7 expression in GC tissues and cell lines. Besides, silenced circATXN7 hampered the proliferation and invasion as well as promoted the apoptosis in GC cells. Moreover, low expression of miR-4319 was found in GC. It was determined that circATXN7 acted as a sponge for miR-4319 and had a negative association with miR-4319. We also found that miR-4319 upregulation restrained GC cell proliferation and migration whereas enhanced apoptosis. Subsequently, ENTPD4, the target gene of miR-4319, was found overexpressed in GC. Additionally, it was negatively correlated with miR-4319 whereas positively associated with circATXN7. In vivo experiments, circATXN7 silence was confirmed to inhibit GC tumor growth. Conclusions:CircATXN7 promoted GC development through sponging miR-4319 and regulating ENTPD4, which identified circATXN7 as a new biomarker in GC.
摘要
背景: 环状 rna (Circular RNAs，circRNAs) 被认为是一类 rna，在基因表达调控和生物过程的发生发展中具有重要意义。然而，circRNA ATXN7 (circATXN7) 的表达谱和分子机制在胃癌 (GC) 中仍大多不确定。 方法: 采用 qRT-PCR 方法检测胃癌组织和细胞中 circATXN7 、 miR-4319 和 ENTPD4 的表达。CCK-8 、集落形成、 EdU 、流式细胞术、 TUNEL 和 transwell 试验评估 circATXN7 或 miR-4319 对细胞增殖、凋亡和侵袭的影响。利用体内试验进一步分析 circATXN7 在 GC 肿瘤发生和进展中的功能。使用荧光素酶报告基因和 RNA 下拉分析验证 miR-4319 和 circATXN7 (或 ENTPD4) 之间的相互作用。 结果: 结果显示在 GC 组织和细胞系中 circATXN7 表达上调。此外，沉默的 circATXN7 抑制了 GC 细胞的增殖和侵袭，促进了细胞凋亡。此外，在 GC 中发现 miR-4319 低表达。确定 circATXN7 作为海绵 miR-4319，与 miR-4319 呈负相关。我们还发现 miR-4319 上调抑制了 GC 细胞的增殖和迁移，而增强了细胞凋亡。随后发现 miR-4319 的靶基因 ENTPD4 在 GC 中过表达。此外，它与 miR-4319 呈负相关，而与 circatxn7 呈正相关。体内实验证实 circATXN7 沉默可抑制 GC 肿瘤生长。 结论: CircATXN7 通过海绵化 miR-4319 和调控 ENTPD4 促进 GC 发育，这确定了 circATXN7 是 GC 中一个新的生物标志物。
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