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首页> 外文期刊>RSC Advances >CircRNA PVT1 modulates cell metastasis via the miR-181a-5p/NEK7 axis and cisplatin chemoresistance through miR-181a-5p-mediated autophagy in non-small cell lung cancer
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CircRNA PVT1 modulates cell metastasis via the miR-181a-5p/NEK7 axis and cisplatin chemoresistance through miR-181a-5p-mediated autophagy in non-small cell lung cancer

机译：CircRNA PVT1通过MIR-181A-5P / NEK7轴和顺铂化学介导通过MIR-181A-5P介导的自噬在非小细胞肺癌中进行调节细胞转移

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In the initiation and evolution of human cancers, circular RNAs (circRNAs) act as crucial regulators. The aim of this report was to ascertain the functional mechanisms of circRNA plasmacytoma variant translocation 1 (circPVT1) in the metastasis and chemoresistance of non-small cell lung cancer (NSCLC). The levels of circPVT1, microRNA-181a-5p (miR-181a-5p) and non-inherited maternal antigens-related kinase 7 (NEK7) were examined via quantitative real-time polymerase chain reaction (qRT-PCR). The levels of the associated proteins were determined through western blot. Cell counting kit-8 (CCK-8) and flow cytometry were used to assess the half inhibitory concentration (IC _(50) ) of cisplatin and cell apoptosis, respectively. Cell invasion was detected by transwell assay. A dual-luciferase reporter assay and RNA immunoprecipitation (RIP) were used to confirm the target relation. The impact of circPVT1 on cisplatin chemoresistance in vivo was investigated using xenograft experiments. CircPVT1 and NEK7 were up-regulated and miR-181a-5p was down-regulated in NSCLC. CircPVT1 knockdown refrained the cisplatin chemoresistance and metastasis of NSCLC cells. MiR-181a-5p was a target of circPVT1 and circPVT1 inhibition alleviated the effects of a miR-181a-5p inhibitor on NSCLC cells. The decrease of circPVT1 accentuated the si-NEK7-inhibited metastasis by the miR-181a-5p/NEK7 axis and relieved the 3-methyladenine (3-MA)-promoted cisplatin chemoresistance by miR-181a-5p-mediated autophagy. Down-regulation of circPVT1 facilitated the cisplatin sensitivity of NSCLC cells in vivo . Due to the modulation of cell metastasis via the miR-181a-5p/NEK7 axis and cisplatin chemoresistance by miR-181a-5p-mediated autophagy in NSCLC, circPVT1 might act as an appreciable therapeutic marker for NSCLC.
机译：在人类癌症的开始和演变中，圆形RNA（Circrnas）充当关键调节因素。本报告的目的是确定非小细胞肺癌（NSCLC）转移和化学率中CircrNA血浆胞瘤变异易位1（CircPVT1）的功能机制。通过定量实时聚合酶链反应（QRT-PCR）检查CirPVT1，MicroRNA-181A-5P（miR-181A-5P）和非遗传母体抗原相关激酶7（NEK7）的水平。通过蛋白质印迹测定相关蛋白质的水平。用于分别评估顺铂和细胞凋亡的半抑制浓度（IC _（50））的细胞计数试剂盒-8（CCK-8）和流式细胞率。通过Transwell测定检测细胞侵袭。使用双荧光素酶报告器测定和RNA免疫沉淀（RIP）来证实目标关系。研究使用异种移植实验研究了CiRCPVT1对体内Cisplatin ChemoLateisce的影响。 CiRCPVT1和NEK7上调，MIR-181A-5P在NSCLC中受到了下调。 CircPVT1敲低抑制了NSCLC细胞的顺铂化学抑制和转移。 miR-181a-5p是CirPVT1的靶标，CirPVT1抑制减轻了MiR-181A-5P抑制剂对NSCLC细胞的影响。 CiRCPVT1的减少突出了MiR-181A-5P / NEK7轴的Si-Nek7抑制转移，并通过MiR-181A-5P介导的自噬释放了3-甲基腺嘌呤（3-MA） - 脯铂Cisplatin Chemocageistis。 CirPVT1的下调促进了体内NSCLC细胞的顺铂敏感性。由于MIR-181A-5P / NEK7轴和通过MIR-181A-5P介导的自噬的CISPLATINChemi制率在NMSCLC中调节细胞转移，CIRCPVT1可以作为NSCLC的可观治疗标记。

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