Furthermore, to gain insight into the biological function of miR-152 overexpression in HCC cells, the 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay, flow cytometric analysis, and the Transwell invasion assay were performed in the constructed cell lines
(data shown in the supporting information). Ectopic miR-152 expression in HCC cells caused an inhibition of cell migration and invasion and BGB324 supplier induced cell apoptosis. However, we did not find any signification role for it in cell proliferation (Supporting Fig. 1). These results indicate that the enhanced expression of miR-152 by gene transfer could reverse the malignant phenotypes of HCC cell lines, and they suggest a tumor-suppressive role and a potential therapeutic target of miR-152. We also believe that these finding have potentially relevant therapeutic implications. The results of this study provide a strong rationale for developing epigenetic therapies that use synthetic miR-152, alone or with other treatments, to reexpress the methylation-silenced TSGs and normalize aberrant patterns of methylation in HBV-related HCC. “
“Background and Aim: Hepatic excessive iron may
play a role in the pathogenesis of non-alcoholic steatohepatitis (NASH). Nrf2 is a master regulator of antioxidative responses. However, the role of Nrf2 in lipid and iron homeostasis remains unclear. Accordingly, it was examined how Nrf2 regulates lipid-related and
iron-regulatory genes after feeding a high-fat diet (HFD) with iron. Methods: Wild-type and Nrf2-null mice were fed the following diets: Selumetinib research buy (i) control diet (4% soybean oil) for 12 weeks, (ii) control diet for 8 weeks followed by control diet containing 0.5% carbonyl iron for 4 weeks, (iii) HFD (4% soybean oil and 16% lard) for 12 weeks, (iv) HFD for 8 weeks followed by HFD containing 0.5% carbonyl iron for 4 weeks. Blood and livers were removed after 12 weeks. Results: Nrf2-null control mice exhibited a tendency towards higher hepatic triglycerides compared to wild-type control mice. Hepatic malondialdehyde was higher and hepatic iron levels Bupivacaine tended to be higher in Nrf2-null mice than wild-type counterparts while on a HFD. The HFD with iron synergistically induced mRNA expression of Pparα targets, including Acox and Cpt1 in wild-type mice, yet the induction was diminished in Nrf2-null mice. Hepatic hepcidin and ferroportin 1 mRNA expression were increased in wild-type mice after feeding a HFD with iron, but were unchanged in any group of Nrf2-null mice. Conclusions: Nrf2 deletion dysregulates hepatic mRNA expression of β-oxidation enzymes and iron-related genes, possibly causing a trend for increased hepatic triglyceride and iron concentrations. Nrf2 may have roles in the progression of NASH. “
“Genome-wide array studies have associated the patatin-like phospholipase domain-containing 3 (PNPLA3) gene polymorphisms with hepatic steatosis.