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Circular RNA PTK2 modifies the progression and radiosensitivity in gastric cancer via miR-369-3p/ZEB1 axis

机译:圆形RNA PTK2通过MiR-369-3P / Zeb1轴修饰胃癌中的进展和放射敏感性

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摘要

Gastric cancer (GC) is one of the common cancers worldwide. Emerging findings imply that aberrant expression of circular RNA_0003221 (circPTK2) is involved in GC. Nevertheless, the function of circPTK2 in GC needs more explanation. Profiles of circPTK2, microRNA (miR)-369-3p, and zinc finger E-box binding homeobox 1 (ZEB1) were determined by quantitative real-time polymerase chain reaction assay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, and transwell assays were employed to estimate cell proliferation, apoptosis, and mobility in GC cells, respectively. Meanwhile, levels of ZEB1 and other indicated proteins were tested using western blot. Survival fraction was assessed utilizing clonogenic assay. Additionally, the role of circPTK2 in tumorigenesis was investigated via a xenograft tumor model. Dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays were conducted to confirm the interrelation between miR-369-3p and circPTK2 or ZEB1. Levels of circPTK2 and ZEB1 were markedly augmented, but miR-369-3p was downregulated in GC tissues and cells. CircPTK2 depletion restrained cell growth, metastasis, and epithelial-mesenchymal transition, and promoted radiosensitivity in GC cells. And circPTK2 depletion reduced tumor growth and metastasis in vivo. Moreover, the effect of circPTK2 silencing on cellular phenotypes and radiosensitivity was regained by miR-369-3p inhibitor. Furthermore, upregulation of ZEB1 could overturn miR-369-3p mimic-induced effect on cell metastasis and radiosensitivity of GC cells. Mechanically, circPTK2 was a sponge of miR-369-3p to separate ZEB1. CircPTK2/miR-369-3p/ZEB1 axis modulated cell behaviors and radiosensitivity in GC; thus circPTK2 might serve as a promising target for GC therapy.
机译:胃癌(GC)是世界上常见的恶性肿瘤之一。新兴的研究结果暗示圆形RNA_0003221(circPTK2)的该异常表达参与GC。然而,circPTK2的GC功能需要更多的解释。 circPTK2,微RNA(MIR)-369-3p和锌指E框结合同源框1(ZEB1)的轮廓通过定量实时聚合酶链式反应测定来确定。 3-(4,5-二甲基吡啶-2-基)-2,5-二苯基溴化四,流式细胞术,和被雇用的transwell测定法来估计细胞的增殖,凋亡,和迁移率在GC细胞,分别。同时,ZEB1和其他指定蛋白质的水平使用免疫印迹试验。存活分数评估利用克隆形成测定。此外,circPTK2在肿瘤发生中的作用通过移植瘤模型进行了研究。双荧光素酶报告,RNA免疫沉淀和RNA Pull-down实验进行了确认的miR-369-3p和circPTK2或ZEB1之间的相互关系。 circPTK2和ZEB1的水平显着增强,但的miR-369-3p在GC组织和细胞中下调。 CircPTK2耗尽抑制细胞生长,转移,和上皮 - 间质转变,并且促进放射敏感性GC细胞。在体内和circPTK2耗尽降低了肿瘤的生长和转移。此外,circPTK2沉默对细胞表型和放射敏感性的影响通过的miR-369-3p抑制剂恢复。此外,ZEB1的上调可以推翻上GC细胞的细胞转移和辐射敏感性的miR-369-3p模拟物诱导的效应。机械,circPTK2是的miR-369-3p的分离ZEB1海绵。 CircPTK2 /的miR-369-3p / ZEB1轴调制细胞行为与放射敏感性GC;因此circPTK2可能作为GC治疗的新靶点。

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  • 来源
    《RSC Advances》 |2020年第3期|共13页
  • 作者单位

    Gansu Prov Hosp Dept Emergency Lanzhou 730000 Gansu Peoples R China;

    Gansu Prov Hosp Dept Nucl Med 204 Donggangxi Rd Lanzhou 730000 Gansu Peoples R China;

    Gansu Prov Hosp Dept Emergency Lanzhou 730000 Gansu Peoples R China;

    Gansu Prov Hosp Dept Emergency Lanzhou 730000 Gansu Peoples R China;

    Gansu Prov Hosp Dept Resp Lanzhou 730000 Gansu Peoples R China;

    Gansu Prov Hosp Dept Radiotherapy Lanzhou 730000 Gansu Peoples R China;

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  • 正文语种 eng
  • 中图分类 化学;
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