P2X7 is important in inflammation and tissue injury. The aim of the present study was to investigate the effect of P2X7 inhibition, using a specific inhibitor (A438079) to prevent the development of liver injury and fibrosis in a mouse model of liver fibrosis. The mouse liver fibrosis model was induced by carbon tetrachloride (CCl4). Mice received subcutaneous administration of vehicle (saline/olive oil), CCl4 or subcutaneous CCl4 and A438079. The pro‑inflammatory and pro‑fibrotic factors were determined by western blot analysis. The biochemistry, histopathology, collagen deposition and nuclear factor‑κB (NF‑κB) activity were also analyzed. Chronic CCl4 treatment resulted in liver injury and collagen accumulation. The expression levels of P2X7, pro‑inflammatory and pro‑fibrotic mediators, and the activity of NF‑κB were markedly increased. Treatment with A438079 significantly inhibited CCl4‑induced P2X7 expression, and attenuated CCl4‑induced liver injury and the inflammatory response. P2X7 blockade also significantly reduced the formation of collagen in the liver and the expression of α-smooth muscle actin and transforming growth factor‑β1. This study demonstrated that P2X7 inhibition attenuated liver injury and fibrosis in a mouse model. Thus, P2X7 is a potential novel therapeutic target for liver injury and fibrosis.

Runt-related transcription factor 2 (RUNX2) was first identified as a transcription factor to play an important role in different biological processes of osteoblast and chondrocyte, including differentiation and migration. Recently, RUNX2 has been implicated in promigratory/proinvasive behavior in different human malignancies. In the present study, we demonstrated that the RUNX2 mRNA and protein expression were both increased significantly in HCC tissues and cell lines. High RUNX2 expression was correlated obviously with poor clinicopathological characteristics including multiple tumor nodes, high histological grading, venous infiltration and advanced tumor-node-metastasis (TNM) stage. In addition, we demonstrated that RUNX2 was a prognostic indicator for predicting 5-year overall survival and disease-free survival of HCC patients. Our studies showed that RUXN2 overexpression promoted, while RUNX2 knockdown inhibited HCC cell migration and invasion in vitro. Notably, RUNX2 positively regulated matrix metalloproteinase 9 (MMP9) accumulation in HCC cells. Furthermore, we confirmed that RUNX2 was positively correlated with MMP9 expression in HCC tissues by Pearson correlation analysis. Mechanistically, we demonstrated that MMP9 overexpression increased HCC cell migration and invasion, while MMP9 knockdown reduced HCC cell migration and invasion in vitro. Alteration of MMP9 expression partially abrogated the effects of RUNX2 on HCC cell migration and invasion, which suggests that RUNX2 developed its pro-metastatic biological function by upregulating the expression of MMP9 in HCC cells. In conclusion, our results reveal that RUNX2 promotes HCC cell migration and invasion by MMP9-mediated pathway, and potentially serves as a new prognostic biomarker and in therapeutic strategies for HCC.

Invasion and metastasis is the main causes leading to the death of hepatocellular carcinoma (HCC) patients. However, the underlying mechanism is still to be explored. Transforming growth factor β1 (TGF-β1) is a stronger inducer of HCC cell invasion. However, the downstream effector of TGF-β1 that promotes HCC invasion is still unknown. In this study, we found that PI3K/Akt activation takes place following the stimulation of TGF-β1. The inhibition of PI3K/Akt activation abolished epithelial-mesenchymal transition (EMT) and invasion of HCC cells induced by TGF-β1. Myocyte enhancer factors 2 (MEF2) family proteins were found to be overexpressed in HCC cells under the treatment of TGF-β1 in a PI3K/Akt-dependent way. Silencing the expression of MEF2s was able to prevent the effect of TGF-β1 on HCC EMT and invasion. Unexpectedly, MEF2 proteins were able to promote the expression of TGF-β1 in HCC cells, suggesting the existence of regulatory circuitry consisting of TGF-β1, PI3K/Akt, and MEF2. A natural compound, oleanolic acid, was demonstrated to suppress the invasion and EMT of HCC cells by downregulating MEF2, showing that targeting this pathway is an effective therapeutic strategy for HCC invasion. We believe that our findings can contribute to better understanding of the involved mechanism of HCC invasion and the development of preventive and therapeutic strategy.

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