Circular RNAs (circRNA) have been reported as regulators involved in 
hepatocellular carcinoma (HCC), but their mechanism of activity remains unknown. 
This study performed quantitative reverse-transcription polymerase chain 
reaction to determine if circNFATC3 was downregulated in 46 paired HCC tissues 
and cell lines. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, 
apoptotic, and transwell assay proved that circNFATC3 can inhibit hepatoma cell 
proliferation, apoptosis, and migration/invasion in vitro. Mouse xenograft assay 
demonstrated that circNFATC3 suppressed tumor size and weight and reduced lung 
metastasis in vivo, and vice versa. The RNA-seq results showed that NFATC3 
itself was the most significantly differentially expressed gene when circNFATC3 
was manipulated, and bioinformatics and luciferase reporter assays verified 
circNFATC3 regulated the expression of NFATC3 by interacting with the 
hsa-miR-548I. Additionally, it was also indicated that the level of NFATC3 was 
downregulated in HCC patients also and was significantly correlated with the 
staging and prognosis of HCC. Moreover, both circNFATC3 and NFATC3 were shown to 
inhibit the phosphorylation of JNK, c-Jun, AKT, and mTOR signaling pathways. 
Overall, the circNFATC3 can sponge miR-548I to protect NFATC3 itself, then it 
regulates hepatoma cell function via the JNK, c-Jun, AKT, and mTOR signaling 
pathways, and the circNFATC3 can be a tumor-repressor on HCC.