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

Chen, Kai; Li, Zhonghu; Zhang, Mengyun; Wang, Bo; Peng, Tao; Shen, Yanbing; Zhang, Jianxin; Ye, Jiaxin; Liu, Yu; Tang, Di; Peng, Minjie; Ma, Dandan; Xiao, Zhengkang; Zhang, Yujun; Jin, Weidong; Li, Xiaowu

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.