Upregulated circular RNA circ_0016760 indicates unfavorable prognosis in NSCLC and promotes cell progression through miR-1287/GAGE1 axis
Upregulated circular RNA circ_0016760 indicates unfavorable prognosis in NSCLC and promotes cell progression through miR-1287/GAGE1 axis
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DOI：
10.1016/j.bbrc.2018.07.164
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发表时间：
2018-09-10
影响因子：
3.1
通讯作者：
Dong, Xiangmei
中科院分区：
文献类型：
--
作者：
Li, Yongsheng;Hu, Jiahang;Dong, Xiangmei
非小细胞肺癌（Non-small cell lung cancer， NSCLC）是一种侵袭性恶性肿瘤，在世界范围内发病率不断上升，其特点是早期复发和转移，预后较差。越来越多的证据表明，异常表达的环状RNA5 （circRNAs）在肿瘤发生中起着关键作用。在目前的研究中，我们关注的是一种新的circRNA circ_0016760在NSCLC中的表达。采用qRT-PCR检测circ_0016760在组织样品和细胞系中的表达水平。并探讨了circ_0016760的临床应用价值。通过CCK-8、菌落形成、流式细胞术、Transwell及动物实验对circ_0016760的功能进行了探索。通过荧光素酶报告基因检测来研究circ_0016760与miR-1287以及miR-1287与GAGE1之间的关联。我们发现circ_0016760在NSCLC组织和细胞中表达增强，circ_0016760表达上调与NSCLC患者TNM晚期分期、淋巴结转移和不良预后相关。此外，circ_0016760能显著促进非小细胞肺癌细胞的生长和转移特性，抑制细胞凋亡。在机制上，circ_0016760作为miR-1287的海绵，调控GAGE1的表达。随后，功能分析表明circ_0016760的致癌特性部分归因于miR-1287/GAGE1轴的调控。综上所述，circ_0016760/miR-1287/GAGE1信号可能在NSCLC的肿瘤发生和进展中发挥重要作用。(C) 2018爱思唯尔公司版权所有。
Non-small cell lung cancer (NSCLC) is an aggressive malignancy with increasing worldwide incidence and is characterized by dismal prognosis due to its early recurrence and metastasis. Accumulating evidence documented that aberrantly expressed circular RNA5 (circRNAs) are critically involved in tumorigenesis. In the current study, we focused on a novel circRNA, circ_0016760 in NSCLC. qRT-PCR was carried out to determine the expression level of circ_0016760 in tissue samples and cell lines. The clinical value of circ_0016760 was also investigated. The functions of circ_0016760 was explored by CCK-8, colony formation, flow cytometry, Transwell and animal experiments. Luciferase reporter assays were conducted to investigate the association between circ_0016760 and miR-1287 and miR-1287 and GAGE1. We found that circ_0016760 was enhanced in NSCLC tissues and cells and the upregulation of circ_0016760 is associated with advanced TNM stages, lymph node metastasis and adverse prognosis in NSCLC patients. Moreover, circ_0016760 could significantly promote cell growth and metastatic properties and inhibit cell apoptosis in NSCLC cells. In mechanism, circ_0016760 functioned as a sponge for miR-1287 and regulated the expression of GAGE1. Subsequently, functional assays illustrated that the oncogenic properties of circ_0016760 is partly attribute to the regulation of miR-1287/GAGE1 axis. In summary, circ_0016760/miR-1287/GAGE1 signaling might play vital roles in the tumorigenesis and progression of NSCLC. (C) 2018 Elsevier Inc. All rights reserved.