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

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

doi:10.1155/2020/1964219

Abstract

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.

Highlights

Hepatocellular carcinoma (HCC) is one of the most common malignancies and ranks as the second most deadly cancer worldwide [1]
The Identified miR-876 Was Expressed at Low Levels in hepatocellular carcinoma (HCC) Cell Lines
We only focused on miR-490 and miR876 since the rest of the miRNAs mentioned above have barely been reported in any study. We found that both miR-490 and miR-876 were expressed at significantly low levels in SMMC-7721 cells compared with L02 cells, a normal liver cell line, but miR-876 was expressed at lower levels than miR-490 in SMMC-7721 cells (Figure 1(a))

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most common malignancies and ranks as the second most deadly cancer worldwide [1]. 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. 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. MiR-876 inhibited the liver cancer progression in in vivo animal assays. MiR-876 and POSTN were inversely correlated in HCC samples and associated with EMT status and liver fibrosis in clinical HCC tissues. 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. MiR-876 inhibited HCC EMT and fibrosis by targeting POSTN, affecting HCC progression and prognosis. Conclusions. miR-876 inhibited HCC EMT and fibrosis by targeting POSTN, affecting HCC progression and prognosis. miR-876 and POSTN may be useful therapeutic targets or prognostic markers of HCC

Methods

Results

Discussion

Conclusion