MiR-595 suppresses cell proliferation and metastasis in hepatocellular carcinoma by inhibiting NF-κB signalling pathway

Abstract

MicroRNAs (miRNAs) have been proven to be critical regulators of cancer development. To date, many of them are still in urgent need of characterisation, and role of miR-595 in hepatocellular carcinoma (HCC) remains unknown. To better understand the mechanism of miR-595 in HCC development, a series of experiments were carried out to explore the effects of miR-595 on malignant behaviour in HCC. First, we found that miR-595 was downregulated in HCC tissues and cells and tightly associated with poor overall survival in HCC patients. Then, we further demonstrated that miR-595 inhibited cell proliferation, migration and invasion in vitro. Additionally, animal experimental results demonstrated that miR-595 inhibited HCC carcinogenesis in vivo. Moreover, we demonstrated that upregulation of miR-595 expression inhibited the NF-κB signalling pathway in HCC cells. To further uncover the molecular mechanism of miR-595 action on the NF-κB signalling pathway, we identified ABCB1 as a direct target of miR-595 through bioinformatics prediction and supported our results with luciferase assays. Finally, we showed that miR-595 inhibited the NF-κB pathway by suppressing ABCB1 expression in HCC cells. Taken together, our findings uncover a pivotal role for the miR-595/ABCB1/NF-κB axis in HCC development, and this novel axis may be a suitable target for diagnostic or therapeutic interventions in HCC.