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The aim of this study was to investigate the effects and mechanisms of hematopoietic-substrate-1-associated protein X-1 (HAX-1) on liver cancer cells. Information on HAX-1 from liver cancer patients was analyzed by the Cancer Genome Atlas (TCGA) program. Cell migration and invasion abilities were respectively tested by scratch assay and transwell assay. Tube formation assay was applied to detect angiogenesis protein and mRNA was determined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. We found that the median month survival of HAX-1 overexpressing liver cancer patients was shorter than that of HAX-1 normal liver cancer patients. HAX-1 was overexpressed in liver cancer tissues and cells, and HAX-1 overexpression promoted the liver cancer cells growth, migration, and invasion, whereas silencing HAX-1 produced the opposite results. Inhibition of Akt by LY294002 reversed the migration and invasion abilities of liver cancer cells, and inhibited the ability of cells growth and angiogenesis. Silencing PIK3CA enhanced the inhibitory effects of HAX-1 silencing on the viability, migration, and invasion of liver cancer cells. HAX-1 affected liver cancer cells metastasis and angiogenesis by affecting Akt phosphorylation and FOXO3A expression. [ABSTRACT FROM AUTHOR]

The effects of harmaline on the viability and apoptosis of human liver carcinoma were investigated in vitro. HepG2 cells were treated with harmaline (0-10 μM), and the proliferation and apoptosis of HepG2 cells were investigated using an MTT assay and flow cytometry, respectively. The protein expression of cellular tumor antigen p53 (p53), cyclin-dependent kinase inhibitor 1 (p21), tumor necrosis factor receptor superfamily member 6 (Fas), Fas ligand (FasL) and caspase-8 was subsequently measured using western blotting. In addition, an ELISA was used to analyze caspase-8/3 activity. Harmaline significantly increased p53, p21, Fas and FasL protein expression in HepG2 cells. Additionally, treatment with harmaline significantly increased the expression of caspase-8 and caspase-8/3 activity. The results from the present study suggest that harmaline suppresses the viability, but induces the apoptosis, of human liver carcinoma cells through upregulation of the p53/p21 and Fas/FasL signaling pathways. [ABSTRACT FROM AUTHOR]

Background: Recent studies have demonstrated that transducin (beta)-like 1 X-linked receptor 1 (TBLR1) is involved in tumor progression. However, the exact role and clinical significance of TBLR1 in hepatocellular carcinoma (HCC) are poorly understood.Aim: In this study, we aimed to investigate the expression and clinical significance of TBLR1 in HCC.Methods: Quantitative polymerase chain reaction and immunohistochemical staining were performed to detect the expression levels of TBLR1 in HCC tissue and adjacent noncancerous tissue (ANT). The relationships between TBLR1 expression and clinicopathological factors were examined in this study. The effects of TBLR1 on epithelial-mesenchymal transition (EMT) of HCC cells were investigated in vitro.Results: The expression levels of TBLR1 were elevated in HCC cell lines. TBLR1 mRNA in HCC tissue was markedly higher (P < 0.001) than that in ANT. High expression of TBLR1 is closely related to serum alpha fetoprotein (P = 0.047), BCLC stage (P < 0.001), maximum size of tumors (P < 0.001), tumor embolus (P < 0.001), and histological grade (P < 0.001). The disease-free survival and overall survival of HCC patients with high expression of TBLR1 were significantly shorter. Furthermore, we found that EMT of HCC cells could be induced by up-regulating TBLR1 and be inhibited by down-regulating TBLR1. ICG-001, the inhibitor of Wnt/β-catenin signaling, could suppress induction of EMT mediated by TBLR1.Conclusions: Our finding suggested that TBLR1 is likely to be a potential prognostic indicator and therapeutic target for HCC and that TBLR1 may be implicated in EMT of HCC cells. [ABSTRACT FROM AUTHOR]

Background: Lysyl oxidase (LOX) is frequently overexpressed in a variety of malignancies and involved in tumor invasion and metastasis. Furthermore, it has been shown that LOX is closely related to vascular endothelial growth factor (VEGF).Aims: In this study, we aimed to investigate the exact role of LOX and the correlation between LOX and VEGF in hepatocellular carcinoma (HCC).Methods: The expression levels of LOX in HCC tissue and adjacent noncancerous tissue were evaluated by quantitative reverse transcription polymerase chain reaction and immunohistochemical analysis. The effect of LOX knockdown on cell proliferation, migration, and invasion was investigated in vitro. The role of LOX in the regulation of VEGF was further characterized in HCC cells that had been treated with transforming growth factor beta (TGF-β).Results: Our study showed that LOX was up-regulated in HCC cell lines and tissue. HCC patients with elevated expression of LOX had relatively shorter disease-free survival and overall survival. Knockdown of LOX reduced the proliferation, migration, and invasion of HCC cells. Additionally, the expression level of LOX positively correlated with that of VEGF. After treatment with TGF-β, the levels of LOX and VEGF were both up-regulated in a dose-dependent manner. In the cells treated with siRNA of LOX, levels of VEGF and phosphorylated p38 were significantly decreased and could not be up-regulated by TGF-β. Inhibition of p38 MAPK signaling abrogated TGF-β-mediated up-regulation of VGEF but did not affect LOX expression.Conclusions: LOX appears to be a predictor of less favorable outcomes and may regulate the expression of VEGF via p38 MAPK signaling. [ABSTRACT FROM AUTHOR]

Background: A quantity of case-control studies have been performed to address the association between three cyclooxygenase-2(COX-2) polymorphisms (-1195G/A, -765G/C and +8473T/C) and the risk of hepatocellular carcinoma (HCC). However, previous research results are inconsistent. We conducted this meta-analysis to clarify the correlation between these COX-2 polymorphisms and HCC risk. Methods: The authors searched in PubMed, EMBASE, Google Scholar, CNKI and WanFang database for relevant articles up to April 28, 2014. The data were extracted by two independent reviewers. Odds ratios (ORs) and 95% confidence intervals were calculated. Results: A total of 8 studies consisting of 2182 cases and 3324 controls were included in this meta-analysis. For COX-2 polymorphism -1195G/A, an association with increased risk was observed under the heterogeneous, homozygous, dominant model. However, COX-2 polymorphisms (-765G/C and +8473T/C) were not related to HCC risk in this study. We also found a similar result in the subgroup analysis of Chinese population that -1195G/A polymorphism, instead of -765G/C or +8473T/C polymorphism, was correlated with the risk of HCC. Conclusions: Polymorphism -1195G/A of COX-2 might be associated with susceptibility to HCC, but no similar correlations were observed between polymorphisms (-765G/C and +8473T/C) and HCC risk. Further large and well-designed studies are required to validate this association. [ABSTRACT FROM AUTHOR]