Circular RNA circCDK13 suppresses cell proliferation, migration and invasion by modulating the JAK/STAT and PI3K/AKT pathways in liver cancer.

Abstract

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 phosphoinositide3-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.