CircPSMC3 suppresses the proliferation and metastasis of gastric cancer by acting as a competitive endogenous RNA through sponging miR-296-5p (Retracted article. See vol. 22, 2023)
CircPSMC3 suppresses the proliferation and metastasis of gastric cancer by acting as a competitive endogenous RNA through sponging miR-296-5p (Retracted article. See vol. 22, 2023)
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CircPSMC3通过海绵miR-296-5p作为竞争性内源RNA抑制胃癌的增殖和转移
DOI：
10.1186/s12943-019-0958-6
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发表时间：
2019-02-18
期刊：
影响因子：
37.3
通讯作者：
Cao, Hongyong
中科院分区：
文献类型：
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作者：
Rong, Dawei;Lu, Chen;Cao, Hongyong
背景：环状rna （circRNAs）是一类具有环状结构的非编码rna，但其功能在很大程度上仍然未知。越来越多的证据表明，环状rna作为功能性rna在恶性疾病的进展中发挥着显著的作用。然而，circrna在胃癌（GC）中的确切作用尚不清楚。方法：采用人circRNA阵列分析和定量逆转录聚合酶反应测定circRNA。采用荧光素酶报告基因、RNA拉下和荧光原位杂交检测circPSMC3与miR-296-5p之间的相互作用。通过异位过表达和sirna介导的circPSMC3敲低、体外增殖、迁移、侵袭及体内转移实验来评价circPSMC3的功能。结果：与正常对照相比，胃癌组织、胃癌患者血浆和胃癌细胞系中CircPSMC3 mRNA表达下调，而非线性PSMC3 mRNA表达下调。GC患者中低circPSMC3表达与较高的TNM分期和较短的总生存期相关。过表达circPSMC3和miR-296-5p抑制剂可在体内和体外抑制胃癌细胞的发生，而共转染circPSMC3和miRNA-296-5p可抵消这一作用。重要的是，我们证明circPSMC3可以作为miR-296-5p的海绵，调节磷酸酶和紧张素同源物（PTEN）的表达，进一步抑制胃癌细胞的肿瘤发生。结论：circPSMC3可作为一种新的潜在循环生物标志物用于GC检测。CircPSMC3通过PTEN擦拭miRNA-296-5p参与胃癌的进展，为胃癌的治疗提供了新的认识。
Background: 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.Methods: 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.Results: 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.Conclusion: 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.