Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
Mol Cancer. 2019 Feb 18;18(1):25. doi: 10.1186/s12943-019-0958-6.
Circular RNAs (circRNAs) are a class of non-coding RNAs with a loop structure, but its functions remain largely unknown. Growing evidence has revealed that circRNAs play a striking role as functional RNAs in the progression of malignant disease. However, the precise role of circRNAs in gastric cancer (GC) remains unclear.
CircRNAs were determined by human circRNA array analysis and quantitative reverse transcription polymerase reaction. Luciferase reporter, RNA pull down, and fluorescence in situ hybridization assays were employed to test the interaction between circPSMC3 and miR-296-5p. Ectopic over-expression and siRNA-mediated knockdown of circPSMC3, proliferation, migration and invasion in vitro, and in vivo experiment of metastasis were used to evaluate the function of circPSMC3.
CircPSMC3 rather than liner PSMC3 mRNA was down-regulated in GC tissues, corresponding plasmas from GC patients as well as GC cell lines compared to normal controls. Lower circPSMC3 expression in GC patients was correlated with higher TNM stage and shorter overall survival. Over-expression of circPSMC3 and miR-296-5p inhibitor could inhibit the tumorigenesis of gastric cancer cells in vivo and vitro whereas co-transfection of circPSMC3 and miRNA-296-5p could counteract this effect. Importantly, we demonstrated that circPSMC3 could act as a sponge of miR-296-5p to regulate the expression of Phosphatase and Tensin Homolog (PTEN), and further suppress the tumorigenesis of gastric cancer cells.
Our study reveals that circPSMC3 can serve as a novel potential circulating biomarker for detection of GC. CircPSMC3 participates in progression of gastric cancer by sponging miRNA-296-5p with PTEN, providing a new insight into the treatment of gastric cancer.
环状 RNA（circRNAs）是一类具有环状结构的非编码 RNA，但它们的功能在很大程度上仍然未知。越来越多的证据表明，circRNAs 在恶性疾病的进展中作为功能性 RNA 发挥着显著的作用。然而，circRNAs 在胃癌（GC）中的确切作用仍不清楚。
通过人类 circRNA 阵列分析和定量逆转录聚合酶链反应确定 circRNAs。利用荧光素酶报告基因、RNA 下拉和荧光原位杂交实验检测 circPSMC3 与 miR-296-5p 之间的相互作用。通过外源性过表达和 siRNA 介导的 circPSMC3 下调、体外增殖、迁移和侵袭以及转移的体内实验来评估 circPSMC3 的功能。
与正常对照组相比，GC 组织、GC 患者的相应血浆以及 GC 细胞系中 circPSMC3 而非线性 PSMC3 mRNA 下调。GC 患者中 circPSMC3 的表达水平较低与较高的 TNM 分期和较短的总生存期相关。circPSMC3 的过表达和 miR-296-5p 抑制剂的共转染可以抑制胃癌细胞在体内和体外的肿瘤发生，而 circPSMC3 和 miRNA-296-5p 的共转染可以抵消这种作用。重要的是，我们证明 circPSMC3 可以作为 miR-296-5p 的海绵来调节磷酸酶和张力蛋白同源物（PTEN）的表达，并进一步抑制胃癌细胞的肿瘤发生。
我们的研究表明，circPSMC3 可以作为 GC 检测的新型潜在循环生物标志物。circPSMC3 通过与 PTEN 海绵吸附 miRNA-296-5p 参与胃癌的进展，为胃癌的治疗提供了新的思路。
