Macrophages Activating Chemokine (C-X-C Motif) Ligand 8/miR-17 Cluster Modulate Hepatocellular Carcinoma Cell Growth And Metastasis

BackgroundEach year,hepatocellular carcinoma is diagnosed in more than half a million people worldwide,Liver cancer is one of the most common malignant tumors in the world.For small liver cancer patients with good liver function,the 5-year survival rate is about 70%after hepatectomy.The development of liver cancer is a complex process.Therefore,to elucidate the molecular mechanism of HCC is helpful to find a better prognostic index,to develop a new treatment strategy for HCC patients,and to break the dilemma of HCC treatment.In recent years,there are more and more studies on the relationship between tumor microenvironment and tumor.The researches suggest that the tumor microenvironment is closely related to the biological behavior of tumor growth,proliferation and metastasis.The tumor microenvironment is the internal environment of the tumor cells,which is closely related to the biological behavior of tumor occurrence,development and metastasis.There are a large number of TAMs in the tumor tissue.There are much more TAMs infiltration and chemokines recruited in the tumor tissue,and TAMs infiltration are highly related to the biological characteristics of the tumor.Macrophages are a major component of the tumor matrix,and macrophages infiltrated in the malignant tumor(such as tumor related macrophages,TAMs)play an important role in hepatocellular carcinoma(HCC).However,the molecular mechanisms of macrophages promoting HCC metastasis is poorly understood.ObjectiveThe aim of the study was to investigate the effects of macrophage chemotaxis and recruitment factor C-X-C motif ligand 8/miR-17 cluster on the proliferation and metastasis of hepatocellular carcinoma(HCC).Methods1.The effects of TAMs on the growth and metastasis of hepatocellular carcinoma(HCC)was studied by tumor associated macrophages and CCK-8 and wound healing assay.2.In order to explore the interaction and mechanism of CXCL8 in TAMs and hepatocellular carcinoma(HCC),we carried out the CCK-8,Transwell test,mi-RNA assay.3.The relationship between the expression of both miR-18a and miR-19a and the clinical characteristics of hepatocellular carcinoma(HCC)was further investigated by cell transfection,cell proliferation assay,RT-PCR and so on.Result1.Macrophages activated by co-cultured liver cancer cells produced higher levels of CXCL8;2.CXCL 8 could be up-regulated in the TAMs environment.3.The expression of miR-18a and miR-19a were increased by CXCL8 in hepatocellular carcinoma.4.The expression of miR-18a and miR-19a was higher than normal tissue in hepatocellular carcinoma.Conclusion1.CXCL8 could improve hepatocellular carcinoma cells growth and metastasis;2.CXCL8 could improve miR-17 cluster expression in the tumor microenvironment,which is related with the mi-RNA expression patterns.3.MiR-18a and miR-19a could enhance Proliferation and metastasis of HCC.4.The expression of miR-18a and miR-19a was highly associated with hepatocellular carcinoma clinical features,which were high expression meaning that the patients’ worse prognosis.