AIM:To study the expression of eukaryotic translation initiation factor 4E(eIF4E),which is closely correlated with malignant tumors,and its relationship to prognosis in hepatocellular carcinoma. METHODS:Western blotti...AIM:To study the expression of eukaryotic translation initiation factor 4E(eIF4E),which is closely correlated with malignant tumors,and its relationship to prognosis in hepatocellular carcinoma. METHODS:Western blotting was performed to quantify the elF4E protein expression in the normal human liver cell line L02 and the hepatoma cell lines Hep3B, HepG2,and Huh7.Forty-six hepatocellular carcinoma samples with complete clinical data were obtained from Changzheng Hospital during the period of December 2008 to July 2009.The expression of eIF4E in the tumor samples and their adjacent tissues were detected by immunohistochemistry.The relationship between the test results and hepatocellular carcinoma(HCC) prognosis was statistically analysed by using a COX proportional hazard model. RESULTS:Western blotting analysis showed that there were distinct eIF4E protein bands in all three of the hepatoma cell lines.In particular,the HepG2 cell line had the highest level of eIF4E protein expression.The L02 cell group had a low eIF4E expression.Immunohistochemical assay showed that there were 32 cases in which the tumour tissue expression was higher than their adjacent tissues,accounting for 69.57%.There were also 14 cases in which the tumour tissue expression was lower or no significant difference was found, accounting for 30.43%.COX proportional hazards model analysis showed that HCC prognosis was related to the depth of invasion,the overexpression of eIF4E and p53, possibly as independent HCC prognostic predictors. CONCLUSION:In summary,eIF4E expression is associated with liver cancer,and patients with high eIF4E expression levels have a higher risk of recurrence.展开更多
Although the clinical manifestations of alcoholic liver disease are well-described, little is known about the molecular basis of liver injury. Recent studies have indicated that ethanol exposure induces global protein...Although the clinical manifestations of alcoholic liver disease are well-described, little is known about the molecular basis of liver injury. Recent studies have indicated that ethanol exposure induces global protein hyperacetylationo This reversible, post- translational modification on the E-amino groups of lysine residues has been shown to modulate multiple, diverse cellular processes ranging from transcriptional activation to microtubule stability. Thus, alcohol- induced protein hyperacetylation likely leads to major physiological consequences that contribute to alcohol-induced hepatotoxicity. Lysine acetylation is controlled by the activities of two opposing enzymes, histone acetyltransferases and histone deacetylases. Currently, efforts are aimed at determining which enzymes are responsible for the increased acetylation of specific substrates. However, the greater challenge will be to determine the physiological ramifications of protein hyperacetylation and how they might contribute to the progression of liver disease. In this review, we will first list and discuss the proteins known to be hyperacetylated in the presence of ethanol. We will then describe what is known about the mechanisms leading to increased protein acetylation and how hyperacetylation may perturb hepatic function.展开更多
Hepatitis C virus (HCV), a positive single-stranded RNA virus, is a major cause of liver disease in humans. Herein we report a novel strategy to inhibit the reproduction and translation of HCV using a short RNA, named...Hepatitis C virus (HCV), a positive single-stranded RNA virus, is a major cause of liver disease in humans. Herein we report a novel strategy to inhibit the reproduction and translation of HCV using a short RNA, named an Additional RNA, to activate the endonuclease activity of Argonaute 2 (Ago2). In the presence of the Additional RNA, the HCV genome RNA has the requisite 12 nucleotides of base-pairing with microRNA-122. This activates the endonuclease activity of Ago2, resulting in cleavage and release of the HCV genome RNA from Ago2 and microRNA-122. The free HCV genome RNA would be susceptible to intracellular degradation, effectively inhibiting its reproduction and translation. This study presents a new method to inhibit HCV that may hold great potential for HCV treatment in the future.展开更多
文摘AIM:To study the expression of eukaryotic translation initiation factor 4E(eIF4E),which is closely correlated with malignant tumors,and its relationship to prognosis in hepatocellular carcinoma. METHODS:Western blotting was performed to quantify the elF4E protein expression in the normal human liver cell line L02 and the hepatoma cell lines Hep3B, HepG2,and Huh7.Forty-six hepatocellular carcinoma samples with complete clinical data were obtained from Changzheng Hospital during the period of December 2008 to July 2009.The expression of eIF4E in the tumor samples and their adjacent tissues were detected by immunohistochemistry.The relationship between the test results and hepatocellular carcinoma(HCC) prognosis was statistically analysed by using a COX proportional hazard model. RESULTS:Western blotting analysis showed that there were distinct eIF4E protein bands in all three of the hepatoma cell lines.In particular,the HepG2 cell line had the highest level of eIF4E protein expression.The L02 cell group had a low eIF4E expression.Immunohistochemical assay showed that there were 32 cases in which the tumour tissue expression was higher than their adjacent tissues,accounting for 69.57%.There were also 14 cases in which the tumour tissue expression was lower or no significant difference was found, accounting for 30.43%.COX proportional hazards model analysis showed that HCC prognosis was related to the depth of invasion,the overexpression of eIF4E and p53, possibly as independent HCC prognostic predictors. CONCLUSION:In summary,eIF4E expression is associated with liver cancer,and patients with high eIF4E expression levels have a higher risk of recurrence.
基金Supported by The National Institute of Alcohol Abuse and Alcoholism (R21 AA015683) awarded to P.L.T.
文摘Although the clinical manifestations of alcoholic liver disease are well-described, little is known about the molecular basis of liver injury. Recent studies have indicated that ethanol exposure induces global protein hyperacetylationo This reversible, post- translational modification on the E-amino groups of lysine residues has been shown to modulate multiple, diverse cellular processes ranging from transcriptional activation to microtubule stability. Thus, alcohol- induced protein hyperacetylation likely leads to major physiological consequences that contribute to alcohol-induced hepatotoxicity. Lysine acetylation is controlled by the activities of two opposing enzymes, histone acetyltransferases and histone deacetylases. Currently, efforts are aimed at determining which enzymes are responsible for the increased acetylation of specific substrates. However, the greater challenge will be to determine the physiological ramifications of protein hyperacetylation and how they might contribute to the progression of liver disease. In this review, we will first list and discuss the proteins known to be hyperacetylated in the presence of ethanol. We will then describe what is known about the mechanisms leading to increased protein acetylation and how hyperacetylation may perturb hepatic function.
基金supported by the National Science Fund for Distinguished Young Scholars (20925520)the National Natural Science Foundation of China (21235003)the Leading Academic Discipline Project of Shanghai Municipal Education Commission (J50108)
文摘Hepatitis C virus (HCV), a positive single-stranded RNA virus, is a major cause of liver disease in humans. Herein we report a novel strategy to inhibit the reproduction and translation of HCV using a short RNA, named an Additional RNA, to activate the endonuclease activity of Argonaute 2 (Ago2). In the presence of the Additional RNA, the HCV genome RNA has the requisite 12 nucleotides of base-pairing with microRNA-122. This activates the endonuclease activity of Ago2, resulting in cleavage and release of the HCV genome RNA from Ago2 and microRNA-122. The free HCV genome RNA would be susceptible to intracellular degradation, effectively inhibiting its reproduction and translation. This study presents a new method to inhibit HCV that may hold great potential for HCV treatment in the future.
