circ_0006988 promotes gastric cancer cell proliferation, migration and invasion through miRNA-92a-2-5p/TFAP4 axis

<b>Aim:</b> To explore precise function and underlying mechanism of circ_0006988 in gastric cancer (GC). <b>Materials &amp; methods:</b> GC tissues were collected clinically, and GC cells were purchased from the company. Quantitative real-time polymerase chain reaction and western blot were used to detect mRNA and protein expression. Functional analysis was performed through CCK-8, Transwell and scratch experiment. Binding relationship was validated through dual luciferase reporter and RNA immunoprecipitation assays. HGC-27 cells were subcutaneously injected into mice to construct a xenograft tumor model. <b>Results:</b> In GC tissues and cells, circ_0006988 overexpressed, promoting proliferation, migration and invasion. MiRNA-92a-2-5p downregulation or <i>TFAP4</i> overexpression weakened effects of circ_0006988 silencing on GC progression. <b>Conclusion:</b> circ_0006988 facilitates GC development through miRNA-92a-2-5p/TFAP4 axis. circ_0006988 was highly expressed in GC tissues and cells, and overexpression of circ_0006988 could promote the proliferation, migration and invasion of gastric cancer (GC) cells. miR-92a-2-5p was mainly located in the cytoplasm of GC cells, and circ_0006988 could interact with miR-92a-2-5p, acting as a sponge to downregulate the expression of miR-92a-2-5p. TFAP4 was upregulated in GC cells. Silencing circ_0006988 reduced the expression of TFAP4, and simultaneously inhibiting the expression of miR-92a-2-5p weakened this effect. Inhibiting miR-92a-2-5p or overexpressing TFAP4 could alleviate the inhibitory effect of silencing circ_0006988 on the malignant progression of GC cells. Silencing circ_0006988 could inhibit the progression of GC in mice.

<b>研究目的：</b> 探讨环状RNA circ_0006988（circular RNA circ_0006988）在胃癌（gastric cancer, GC）中的精准功能及潜在作用机制。<b>材料与方法：</b> 临床收集胃癌组织，从商业公司购得胃癌细胞系。采用实时定量聚合酶链反应（quantitative real-time polymerase chain reaction, qRT-PCR）与蛋白质印迹（western blot）分别检测mRNA与蛋白的表达水平。通过CCK-8实验、Transwell实验及划痕实验开展功能分析。通过双荧光素酶报告基因实验与RNA免疫沉淀实验验证二者的结合关系。将HGC-27细胞皮下注射至小鼠体内，构建异种移植瘤模型。<b>结果：</b> 在胃癌组织与细胞中，环状RNA circ_0006988呈高表达，可促进细胞增殖、迁移与侵袭。下调微小RNA-92a-2-5p（microRNA-92a-2-5p, miR-92a-2-5p）的表达或过表达转录因子AP-4（TFAP4），可削弱circ_0006988沉默对胃癌进展的抑制作用。<b>结论：</b> 环状RNA circ_0006988通过调控miR-92a-2-5p/TFAP4轴促进胃癌发生发展。环状RNA circ_0006988在胃癌组织及细胞中呈高表达，其过表达可促进胃癌细胞的增殖、迁移与侵袭。miR-92a-2-5p主要定位于胃癌细胞的细胞质中，环状RNA circ_0006988可与miR-92a-2-5p结合，通过海绵吸附作用下调其表达。TFAP4在胃癌细胞中呈高表达。沉默circ_0006988可降低TFAP4的表达水平，同时抑制miR-92a-2-5p的表达可削弱这一效应。抑制miR-92a-2-5p的表达或过表达TFAP4，可缓解circ_0006988沉默对胃癌细胞恶性进展的抑制作用。沉默circ_0006988可在小鼠体内抑制胃癌的进展。