Background Abnormally expressed circular RNAs (circRNAs) are implicated in the development and treatment of gastric cancer (GC). Previous study has reported that hsa_circ_0003159 is expressed in GC. However, the role and mechanism of hsa_circ_0003159 in GC progression remain unclear. Methods GC tissues and normal tissues were harvested from 55 patients in this study. The levels of hsa_circ_0003159, microRNA (miR)-223-3p and N-myc downstream regulated gene 1 (NDRG1) were measured by quantitative real-time polymerase chain reaction or western blot. Cell proliferation, migration, invasion and apoptosis were determined by cell counting kit (CCK)-8, transwell assay, flow cytometry and western blot, respectively. The target association of miR-223-3p-hsa_circ_0003159 and miR-223-3p-NDRG1 was explored by dual-luciferase reporter assay. Xenograft model was established to assess the roles of hsa_circ_0003159 in GC in vivo. Results Hsa_circ_0003159 was lowly expressed in GC tissues and cells and mainly presented in the cytoplasm. Low expression of hsa_circ_0003159 was associated with lower overall survival and disease-free survival. Hsa_circ_0003159 overexpression inhibited proliferation, migration and invasion but induced apoptosis in GC cells. MiR-223-3p was a target of hsa_circ_0003159 and abated the effect of hsa_circ_0003159 on proliferation, migration, invasion and apoptosis in GC cells. Hsa_circ_0003159 promoted NDRG1 expression by competitively sponging miR-223-3p. Knockdown of NDRG1 reversed the suppressive effect of hsa_circ_0003159 on GC progression. Besides, hsa_circ_0003159 decreased GC cell xenograft tumor growth by regulating miR-223-3p and NDRG1. Conclusion Hsa_circ_0003159 suppressed proliferation, migration, invasion and xenograft tumor growth but promoted apoptosis by decreasing miR-223-3p and increasing NDRG1 in GC, indicating a novel target for treatment of GC.

中文翻译：

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Hsa_circ_0003159 通过调节 miR-223-3p/NDRG1 轴抑制胃癌进展。

背景 异常表达的环状 RNA (circRNA) 与胃癌 (GC) 的发生和治疗有关。以前的研究报告说，hsa_circ_0003159 在 GC 中表达。然而，hsa_circ_0003159 在 GC 进展中的作用和机制仍不清楚。方法 本研究采集 55 例患者的 GC 组织和正常组织。通过定量实时聚合酶链反应或蛋白质印迹测量 hsa_circ_0003159、microRNA (miR)-223-3p 和 N-myc 下游调节基因 1 (NDRG1) 的水平。细胞增殖、迁移、侵袭和凋亡分别采用细胞计数试剂盒（CCK）-8、transwell检测、流式细胞术和western blot检测。通过双荧光素酶报告基因分析探索了 miR-223-3p-hsa_circ_0003159 和 miR-223-3p-NDRG1 的靶标关联。建立异种移植模型以评估 hsa_circ_0003159 在体内 GC 中的作用。结果 Hsa_circ_0003159在GC组织和细胞中低表达，主要存在于细胞质中。hsa_circ_0003159 的低表达与较低的总生存期和无病生存期相关。Hsa_circ_0003159 过表达抑制了 GC 细胞的增殖、迁移和侵袭，但诱导了细胞凋亡。MiR-223-3p 是 hsa_circ_0003159 的靶点，可减弱 hsa_circ_0003159 对 GC 细胞增殖、迁移、侵袭和凋亡的影响。Hsa_circ_0003159 通过竞争性海绵化 miR-223-3p 促进 NDRG1 的表达。敲除 NDRG1 逆转了 hsa_circ_0003159 对 GC 进展的抑制作用。此外，hsa_circ_0003159 通过调节 miR-223-3p 和 NDRG1 来降低 GC 细胞异种移植肿瘤的生长。