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ABSTRACT: Hepatocellular carcinoma is one of the most common and lethal cancers worldwide, especially in developing countries. In the present study, we found that the expression of a microRNA, miR-590-5P, was down-regulated and S100A10 was up-regulated in six hepatocellular carcinoma cell lines. The reporter gene assay showed that overexpression of miR-590-5P effectively reduced the activity of luciferase expressed by a vector bearing the 3' untranslated region of S100A10 mRNA. Ectopic miR-590-5P overexpression mediated by lentiviral infection decreased expression of S100A10. Infection of Lv-miR-590-5P inhibited cell growth and induced cell cycle G1 arrest in HepG2 cells. In addition, miR-590-5P expression suppressed the expression of Wnt5a, cMyc and cyclin D1, and increased the phosphorylation of β-catenin and expression of Caspase 3, which may contribute to the inhibitory effect of miR-590-5P on cell growth. Taken together, our data suggest that down-regulation of miR-590-5P is involved in hepatocellular carcinoma and the restoration of miR-590-5P can impair the growth of cancer cells, suggesting that miR-590-5P may be a potential target molecule for the therapy of hepatocellular carcinoma.
International Journal of Molecular Sciences 01/2013; 14(4):8556-8569. · 2.60 Impact Factor
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ABSTRACT: Bax-interacting factor-1 (Bif-1) interacts with Beclin1 [the mammalian ortholog of yeast autophagy-related gene 6 (Atg6)] and affects the formation of autophagosomes during autophagy. The aim of this study was to explore Bif-1 expression and its prognostic significance in comparison with various clinicopathological predictors of survival. Bif-1 protein expression was determined by immunohistochemistry in 206 hepatocellular carcinomas. Cytoplasmic immunoreactivity was scored semi-quantitatively. The results were analyzed in correlation with various clinicopathological characteristics, including patient survival. The Chi-square test and Kaplan-Meier survival analysis were applied. The expression of Bif-1 was significantly higher in the hepatocellular cancers than in the adjacent matched non-tumor tissues (51.5 vs. 33.0%, P<0.01). Increased expression of Bif-1 in hepatocellular carcinomas was significantly correlated with a low grade of differentiation and a shortened overall survival (P<0.05). No significant differences were found between the expression of Bif-1 and age, gender, tumor size, damage of capsule, expression of hepatitis B surface antigen (HBs-Ag) and portal venous invasion. Our data demonstrated that Bif-1 is frequently expressed in hepatocellular carcinoma. Overexpression of Bif-1 is a new independent prognostic marker, which is associated with poor differentiation as well as shortened overall survival.
Oncology letters 04/2012; 3(4):851-854. · 0.11 Impact Factor
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ABSTRACT: Apocynin is a widely used antioxidant in both basic and clinical research. The current study aimed to investigate the protective effect of apocynin in an established alcoholic steatohepatitis rat model. Healthy SD rats were gastrically fed with ethanol (4.0 g/kg) for 8 weeks to induce alcoholic steatohepatitis. After 8 weeks, rats were fed with ethanol for another 2 weeks with or without a daily intraperitoneal injection of 25 mg/kg apocynin. After sacrificing, serum and liver samples were subjected to hepatic injury measurements. After 8-week ethanol induction, rats exhibited typical alcoholic steatohepatitis features including reduced body weight, hepatic histological changes, elevated serum alanine transaminase (ALT) level, increased levels of oxidative stress and inflammatory markers, NADPH oxidases, and renin-angiotensin system (RAS) marker. Co-treatment of apocynin alleviated the hepatic injury and biochemical parameters induced by alcoholic steatohepatitis. In conclusion, addition of apocynin significantly attenuates hepatic oxidative stress and inflammation induced by alcoholic steatohepatitis. This effect is partly through the inhibition of the RAS system.
Immunopharmacology and Immunotoxicology 01/2012; 34(4):633-8. · 1.83 Impact Factor
