Circular RNA circCDK13 suppresses cell proliferation, migration and invasion by modulating the JAK/STAT and PI3K/AKT pathways in liver cancer
Circular RNA circCDK13 suppresses cell proliferation, migration and invasion by modulating the JAK/STAT and PI3K/AKT pathways in liver cancer
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DOI：
10.3892/ijo.2018.4371
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发表时间：
2018-07-01
影响因子：
5.2
通讯作者：
Huang, Ming-Sheng
中科院分区：
文献类型：
--
作者：
Lin, Qu;Ling, Yun-Biao;Huang, Ming-Sheng
环状RNA最近被公开为人类癌症的潜在生物标志物。本研究旨在表征新型环状 RNA（circCDK13）在肝癌进展中的表达和功能，并阐明其潜在机制。为此，通过 RT-PCR 定量分析了各种肝癌细胞系和人类癌组织中的 circCDK13 表达。通过3-(4,5-二甲基噻唑-2-基)-5-(3-羧甲氧基苯基)-2-(4-磺苯基)-2H-四唑、内盐(MTS)测定、流式细胞术和Transwell培养系统评估circCDK13表达增强的肝癌细胞的迁移、细胞周期进展、增殖和侵袭。进行微阵列和蛋白质印迹分析以探索潜在的信号传导机制。最后通过裸鼠致瘤性实验检测了circCDK13在肝癌中的作用。结果显示，在各种肝癌细胞系和肝癌（肝细胞癌）患者的组织样本中，circCDK13 表达受到抑制。肝癌细胞中诱导的 circCDK13 过度表达显着抑制其迁移率，改变细胞周期进程，并抑制细胞迁移和侵袭能力。微阵列分析还鉴定了许多受 circCDK13 调节的下游基因，特别是 Janus 酪氨酸激酶 (JAK)/信号转导和转录激活因子 (STAT) 和磷酸肌醇 3-激酶 (PI3K)/AKT 信号通路中的基因。致瘤性测定结果显示，circCDK13过表达可显着抑制裸鼠肝癌进展。总的来说，本研究的结果表明，circCDK13是一种新型环状RNA，可以抑制肝癌进展，并且这些抑制作用可能是通过JAK/STAT和PI3K/AKT信号通路介导的。
Circular RNAs have recently been disclosed as potential biomarkers for human cancers. This study aimed to characterize the expression and function of a novel circular RNA, circCDK13, in liver cancer progression, as well as to elucide the underlying mechanisms. For this purpose, circCDK13 expression was quantitatively analyzed by RT-PCR in various liver cancer cell lines and human cancerous tissues. The migration, cell cycle progression, proliferation and invasion of liver cancer cells with an enhanced circCDK13 expression were evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay, flow cytometry and the Transwell culture system. Microarray and western blot analyses were performed to explore the underlying signaling mechanisms. The role of circCDK13 in liver cancer was finally examined by tumorigenicity assay using nude mice. The results revealed that circCDK13 expression was suppressed in various liver cancer lines and tissue samples from patients with liver cancer (hepatocellular carcinoma). The induced overexpression of circCDK13 in the liver cancer cells markedly inhibited their migration rates, altered cell cycle progression, and suppressed the cell migratory and invasive capacities. Microarray analysis also identified numerous downstream genes regulated by circCDK13, particularly those in the Janus tyrosine kinase (JAK)/signal transducer and activator of transcription (STAT) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. The results of the tumorigenicity assay revealed that circCDK13 overexpression significantly inhibited liver cancer progression in nude mice. On the whole, the findings of this study indicate that circCDK13 is a novel circular RNA that suppresses liver cancer progression, and that these suppressive effects are possibly mediated via the JAK/STAT and PI3K/AKT signaling pathways.