PDF(Pubmed)
Abstract：
Background: An increasing number of studies have demonstrated that differentially expressed circular RNAs (circRNAs) play critical roles in carcinogenesis. However, the biological function and clinical significance of hsa_circ_0005927 during gastric carcinogenesis remain unclear. The aim of this study was to investigate the acting mechanism and clinical significance of hsa_circ_0005927 in the invasion and metastasis of gastric cancer (GC). Methods: Hsa_circ_0005927 was detected in GC tissues, plasma and gastric juice from patients with GC, and its correlations with clinicopathological parameters were investigated. Receiver operating characteristic curves, Kaplan-Meier survival curves and a prognostic nomogram model were generated to analyze the diagnostic and prognostic value. Real-time cell analyzer, plate colony formation, and Transwell migration and invasion assays were utilized to assess GC cell proliferation, migration and invasion, respectively. Nucleoplasmic separation was applied to determine the distribution of hsa_circ_0005927 in cells. TargetScan and miRanda software were used for target microRNA (miRNA) prediction. Transcriptome sequencing and bioinformatics analysis were performed to annotate the functions of hsa_circ_0005927 in gastric carcinogenesis and metastasis from an RNomic perspective. Key target genes and immune cell infiltrations were analysed. Results: Hsa_circ_0005927 was found downregulated in high-grade intraepithelial neoplasia (HGIEN) tissues and GC tissues. Hsa_circ_0005927 levels in GC tissues were negatively correlated not only with lymphatic metastasis and distal metastasis but also with overall survival and disease-free survival. As a screening biomarker for GC, plasma hsa_circ_0005927 levels significantly increased in the early stages of GC, with a sensitivity and specificity of 52.38% and 76.19%, respectively. Hsa_circ_0005927 was mainly distributed in the cytoplasm, and structurally, it possesses multiple miRNA response elements (MREs) that interact with five miRNAs. A total of 421 downstream target genes of hsa_circ_0005927 were identified by transcriptome sequencing; and bioinformatics analysis suggested that these genes were involved mainly in the negative regulation of the T-cell apoptotic process, the interleukin-27-mediated signaling pathway, growth factor activity, guanylate cyclase activity, transcriptional misregulation in cancer, the cGMP-PKG signaling pathway, and the GnRH signaling pathway during gastric carcinogenesis and metastasis. GUCY1A2 and STK32A are key target genes significantly associated with immune infiltration. Conclusion: Our study revealed that hsa_circ_0005927 is a new player related to the invasion and metastasis of GC and is a potential indicator for early GC screening.
摘要：
背景：越来越多的研究表明，差异表达的环状RNA（circRNAs）在致癌作用中起着关键作用。然而,hsa_circ_0005927在胃癌发生过程中的生物学功能和临床意义尚不清楚。本研究的目的是探讨hsa_circ_0005927在胃癌（GC）侵袭和转移中的作用机制和临床意义。方法:在GC组织中检测Hsa_circ_0005927,来自GC患者的血浆和胃液，并研究其与临床病理参数的相关性。接收机工作特性曲线,生成Kaplan-Meier存活曲线和预后列线图模型以分析诊断和预后价值。实时细胞分析仪，平板集落形成，和Transwell迁移和侵袭试验用于评估GC细胞增殖，移民和入侵，分别。应用核质分离来确定hsa_circ_0005927在细胞中的分布。TargetScan和miRanda软件用于靶微小RNA(miRNA)预测。进行转录组测序和生物信息学分析，以从RNA组学角度注释hsa_circ_0005927在胃癌发生和转移中的功能。分析了关键靶基因和免疫细胞浸润。结果：发现Hsa_circ_0005927在高级别上皮内瘤变（HGIEN）组织和GC组织中下调。GC组织中Hsa_circ_0005927水平不仅与淋巴转移和远端转移呈负相关，而且与总生存期和无病生存期呈负相关。作为GC的筛选生物标志物，血浆hsa_circ_0005927水平在GC的早期阶段显着增加，敏感性和特异性分别为52.38%和76.19%，分别。Hsa_circ_0005927主要分布在细胞质中,在结构上，它具有与5个miRNA相互作用的多个miRNA应答元件(MRE)。通过转录组测序，共鉴定出421个hsa_circ_0005927下游靶基因；生物信息学分析表明，这些基因主要参与T细胞凋亡过程的负调控。白细胞介素-27介导的信号通路，生长因子活性，鸟苷酸环化酶活性，癌症中的转录失调，cGMP-PKG信号通路，胃癌发生和转移过程中的GnRH信号通路。GUCY1A2和STK32A是与免疫浸润显著相关的关键靶基因。结论：我们的研究表明，hsa_circ_0005927是与GC侵袭和转移相关的新参与者，是早期GC筛查的潜在指标。
