Circular RNA circGRAMD1B inhibits gastric cancer progression by sponging miR-130a-3p and regulating PTEN and p21 expression
Circular RNA circGRAMD1B inhibits gastric cancer progression by sponging miR-130a-3p and regulating PTEN and p21 expression
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DOI：
10.18632/aging.102414
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发表时间：
2019-11-15
期刊：
影响因子：
5.2
通讯作者：
Wang, Ziwei
中科院分区：
文献类型：
--
作者：
Dai, Xinglong;Guo, Xiong;Wang, Ziwei
环状RNA（circRNA）已成为各种癌症的重要调控因子和生物标志物。然而，一种名为circGRAMD 1B的新型circRNA在人类胃癌（GC）中的作用仍不清楚。使用微阵列来筛选GC中的circRNA表达。实时荧光定量PCR检测circGRAMD 1B的表达。进行功能获得和丧失实验以研究circGRAMD 1B在体外和体内的生物学功能。通过生物信息学分析、荧光原位杂交、双荧光素酶报告基因分析、RNA免疫沉淀、RNA pull-down分析和拯救实验等方法，验证了竞争性内源RNA（ceRNA）的作用机制。我们筛选了差异表达的circRNA，发现circGRAMD 1B在GC组织和细胞系中表达下调。在功能上，circGRAMD 1B作为抑癌基因，抑制GC细胞的增殖、迁移和侵袭能力。然后，我们验证了circGRAMD 1B在GC细胞中充当靶向miR-130 a-3 p的海绵; circGRAMD 1B通过靶向miR-130 a-3 p减轻GC细胞增殖、迁移和侵袭。机制分析表明，PTEN和p21参与了circGRAMD 1B/miR-130 a-3 p轴抑制GC肿瘤发生。我们的研究结果表明，circGRAMD 1B通过调节miR-130 a-3 p-PTEN/p21在GC进展中起重要作用，这可能为GC提供潜在的生物标志物和治疗靶点。
Circular RNAs (circRNAs) have emerged as essential regulators and biomarkers of various cancers. However, the effects of a novel circRNA termed circGRAMD1B in human gastric cancer (GC) remain unclear. A microarray was used to screen circRNA expression in GC. Quantitative real-time PCR was used to detect the expression of circGRAMD1B. Gain- and loss-of-function experiments were performed to investigate the biological functions of circGRAMD1B in vitro and vivo. Bioinformatics analysis, fluorescence in situ hybridization, dual-luciferase reporter assay, RNA immunoprecipitation, RNA pull-down assay, and rescue experiments were conducted to confirm the underlying mechanisms of competitive endogenous RNAs (ceRNAs). We screened differentially expressed circRNAs and found that circGRAMD1B expression was downregulated in GC tissues and cell lines. Functionally, circGRAMD1B acted as an anti-oncogene and inhibited the proliferation, migration, and invasion abilities of GC cells. Then, we verified that circGRAMD1B served as a sponge that targeted miR-130a-3p in GC cells; circGRAMD1B alleviated GC cell proliferation, migration, and invasion by targeting miR-130a-3p. A mechanistic analysis showed that PTEN and p21 were involved in circGRAMD1B/miR-130a-3p axis-inhibited GC tumorigenesis. Our findings suggest that circGRAMD1B plays an important role in GC progression by regulating miR-130a-3p-PTEN/p21, which may provide a potential biomarker and therapeutic target for GC.