miR-876 Inhibits EMT and Liver Fibrosis via POSTN to Suppress Metastasis in Hepatocellular Carcinoma

BACKGROUND: The asymptomatic onset, frequent recurrence, and poor prognosis of hepatocellular carcinoma (HCC) prompted us to identify new therapeutic targets or predictive markers of HCC diagnosis or prognosis. METHODS: In this study, bioinformatics analysis was used to screen for target miRNAs from the open-access TCGA database. Transwell assays, Western blotting, and qRT-PCR analyses were used to detect cellular functions and gene expression in HCC cells and samples. A nude mouse tumorigenesis model was established to facilitate the observation of HCC progression. Other assays included luciferase reporter assays, IHC, and survival analysis. RESULTS: We found that the identified miR-876 from TCGA was expressed at low levels in HCC cell lines and that low miR-876 expression was corrected with liver cirrhosis, tumor thrombus, and TNM stage. Further research revealed that miR-876 regulated cell invasion, EMT, and collagen expression by targeting POSTN expression. miR-876 and POSTN were inversely correlated in HCC samples and associated with EMT status and liver fibrosis in clinical HCC tissues. miR-876 inhibited the liver cancer progression in in vivo animal assays. Finally, both miR-876 and POSTN were risk factors for HCC survival, and HCC patients with combined low miR-876 and high POSTN expression had worse prognosis. CONCLUSIONS: miR-876 inhibited HCC EMT and fibrosis by targeting POSTN, thus affecting HCC progression and prognosis. miR-876 and POSTN may be useful therapeutic targets or prognostic markers of HCC.