Wang Jingyu, Lv Weize, Lin Zhidong, Wang Xiao, Bu Juyuan, Su Yonghui
1Department of Gastrointestinal Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, No. 52, East Meihua Road, Zhuhai, 519000 Guangdong China.
2Department of Thoracic Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China.
Cancer Cell Int. 2020 Feb 19;20:57. doi: 10.1186/s12935-020-1119-0. eCollection 2020.
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.
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.
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.
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.
异常表达的环状RNA（circRNA）与胃癌（GC）的发生发展及治疗相关。既往研究报道hsa_circ_0003159在胃癌中表达。然而，hsa_circ_0003159在胃癌进展中的作用及机制仍不清楚。
本研究收集了55例患者的胃癌组织和正常组织。采用定量实时聚合酶链反应或蛋白质免疫印迹法检测hsa_circ_0003159、微小RNA（miR）-223-3p和N-myc下游调节基因1（NDRG1）的水平。分别通过细胞计数试剂盒（CCK）-8法、Transwell实验、流式细胞术和蛋白质免疫印迹法检测细胞增殖、迁移、侵袭和凋亡情况。采用双荧光素酶报告基因实验探究miR-223-3p与hsa_circ_0003159以及miR-223-3p与NDRG1之间的靶向关系。建立异种移植模型以评估hsa_circ_0003159在体内对胃癌的作用。
hsa_circ_0003159在胃癌组织和细胞中低表达，主要定位于细胞质。hsa_circ_0003159低表达与较低的总生存期和无病生存期相关。hsa_circ_0003159过表达抑制胃癌细胞的增殖、迁移和侵袭，但诱导其凋亡。miR-223-3p是hsa_circ_0003159的靶点，可减弱hsa_circ_0003159对胃癌细胞增殖、迁移、侵袭和凋亡的影响。hsa_circ_0003159通过竞争性结合miR-223-3p促进NDRG1表达。敲低NDRG1可逆转hsa_circ_0003159对胃癌进展的抑制作用。此外，hsa_circ_0003159通过调节miR-223-3p和NDRG1降低胃癌细胞异种移植瘤的生长。
hsa_circ_0003159通过降低miR-223-3p水平和增加NDRG1表达抑制胃癌细胞的增殖、迁移、侵袭及异种移植瘤生长，但促进其凋亡，提示其可能是胃癌治疗的新靶点。
