42, 43 For HCC, aberrant expression of N-cadherin has been associ

42, 43 For HCC, aberrant expression of N-cadherin has been associated with invasiveness of carcinoma cells and poor prognosis.44 JNK inhibitor Furthermore, some reports have suggested that N-cadherin can promote primary liver tumor growth and exerts antiapoptotic effects on HCC cells.45, 46 Therefore, regulation of N-cadherin by miR-194 may play an important and multifaceted role in cancer progression. It is still unclear what factors maintain the high expression of miR-194 in the liver. In the small intestine, miR-194 is transcriptionally up-regulated by a gastrointestinal

tract–enriched nuclear receptor, hepatic nuclear factor 1α (HNF1α).15 HNF1α is abundantly expressed in hepatocytes. Therefore, HNF1α is probably a regulator of miR-194

expression in hepatocytes, and disruption of HNF1α transactivation on miR-194 may potentiate metastatic capacities of primary JQ1 liver tumor cells. Consistent with this notion, HNF1α expression is repressed in more invasive liver tumor cells.47 In addition, p53 activation also induces a significant increase of miR-194 expression in tumor cell lines.48 Considering the prominent role of p53 in preventing metastasis,49 the induction of miR-194 by p53 may represent a protective or self-controlling mechanism in tumor progression. It should be noted that p53 family members (p53, p63, and p73) are known to regulate ZEB1 expression,50 and both HNF1α and p53 activate miR-192 and miR-215, which are in the same cluster with miR-194 in mammalian genomes.15, 48 In addition, miR-192 and miR-215 can directly target ZEB1/2 Selleck Abiraterone and have been suggested to affect kidney fibrosis,51 which also undergoes an EMT-like process. Therefore, it is possible that miR-194 may work together with miR-192 and miR-215 in regulating EMT or mesenchymal-to-epithelial transition. In conclusion, our results suggest that miR-194 is a potential hepatic miRNA marker for epithelial cells, and that it plays an antimetastatic role in primary liver tumor cells. Therefore, miR-194 is a potential target for HCC prognosis and therapy. We thank Kurt Jenkins for manuscript proofreading. We also thank Xiaoqiong Wang for

pathological analysis and Chang-Zheng Chen for providing the MDH1-PGK-eGFP-2.0 plasmid. Additional Supporting Information may be found in the online version of this article. “
“Aim:  Sorafenib is the first small molecule with significant clinical activity for advanced hepatocellular carcinoma (HCC). However, intolerable adverse events are sometimes observed. On the other hand, it has been reported that some toxicities of molecular targeted drugs, such as skin toxicities and arterial hypertension, are correlated with good clinical outcomes in other cancers. Methods:  We identified the correlations between adverse events and prognosis for sorafenib therapy in all patients with HCC treated at the institutions of the Saga Liver Cancer Study Group.

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