Circular RNA circC3P1 suppresses hepatocellular carcinoma growth and metastasis through miR-4641/PCK1 pathway

Abstract In the recent years, increasing evidences identify circular RNAs (circRNAs) as a class of important regulators in various human cancers. Nevertheless, the functions and mechanisms of most circRNAs in cancer cells remain largely unknown. In this study, we found out a significantly downregulated circRNA circC3P1 in hepatocellular carcinoma (HCC) tissues compared to adjacent normal tissues. And our results indicated that circC3P1 expression level was negatively correlated with TNM stage, tumor size and vascular invasion in HCC. Moreover, we found that circC3P1 overexpression dramatically inhibited the proliferation, migration and invasion of HCC cells in vitro and in vivo . In terms of mechanism, we found that circC3P1 could promote PCK1 expression through sponging miR-4641 in HCC cells. We showed that miR-4641 expression was negatively correlated with that of either circC3P1 or PCK1 in HCC tissues. Finally, by functional experiments, we demonstrated that knockdown of PCK1 significantly attenuated the effects of circC3P1 overexpression on HCC cell proliferation, migration and invasion. In summary, our findings illustrated that circC3P1 acts as a tumor suppressor via enhancing PCK1 expression by sponging miR-4641 in HCC.