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Objective:To investigate the expression and clinical significance of histone acetyltransferase P300 in hepatocellular carcinoma.Methods:From January 2013 to December 2017, surgical specimens of 100 patients with hepatocellular carcinoma were collected from the Department of General Surgery of Sichuan Mianyang 404 Hospital. The expressions of P300, CD90, alpha fetoprotein (AFP), Ki-67 and CD34 in hepatocellular carcinoma tissue were detected. At the same time, 42 hepatic hemangioma specimens and 56 liver tissue specimens with moderate to severe liver cirrhosis were collected, and the positive expression rate of P300 in tissues was detected. The correlations between the expression of P300 and clinicopathological features and prognosis of patients with hepatocellular carcinoma were analyzed.Results:The positive expression rates of P300 in normal liver tissue, liver cirrhosis tissue and hepatocellular carcinoma tissue increased gradually, which were 11.9% (5/42), 32.1% (18/56) and 57.0% (57/100) respectively, with a statistically significant difference ( χ2=27.192, P<0.001). Tumor grade ( χ2=9.337, P=0.009), T stage ( χ2=8.794, P=0.032), clinical TNM stage ( χ2=6.121, P=0.013), AFP ( χ2=11.040, P=0.001), CD90 ( χ2=9.903, P=0.002), CD34 ( χ2=4.066, P=0.044) significantly affected the expression of P300. Spearman rank correlation analysis showed that the abnormal expression of P300 was positively correlated with the expression of AFP ( r=0.335, P=0.001), CD90 ( r=0.328, P=0.002) and CD34 ( r=0.264, P=0.047) , but had no significant correlation with the expression of Ki-67 ( P>0.05). Survival analysis showed that the 5-year survival rate of patients with P300 positive expression was 17.6%, and that of patients with P300 negative expression was 62.5%, and there was a statistically significant difference ( χ2=10.596, P<0.001). Cox multivariate analysis showed that P300 positive expression ( RR=2.554, 95% CI: 1.261-4.502, P=0.009), CD90 positive expression ( RR=3.574, 95% CI: 1.021-11.980, P=0.030) and TNM Ⅱ-Ⅳ stage ( RR=0.332, 95% CI: 0.105-0.596, P=0.002) were independent risk factors for poor prognosis of patients with hepatocellular carcinoma. Conclusion:The positive expression of P300 is closely related to the occurrence of hepatocellular carcinoma and can be used as an independent factor to judge the poor prognosis of patients with hepatocellular carcinoma.
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Lysine acetylation has emerged as one of the most important post-translational modifications that participates in various biological and pathological processes. Histone acetyltransferase 1 (HAT1) as the first identified protein ε-amino lysine acetyltransferase is able to regulate the acetylation of histones and non-histone proteins. However‚ the acetylation substrates and sites mediated by HAT1 in liver cancer are poorly understood. In this study‚ we demonstrated that HAT1 was highly expressed in the liver cancer tissues‚ which was negatively associated with the prognosis of patients. Based on the establishment of the HAT1-knockout HepG2 cell line‚ we employed a quantitative proteomics approach to study the profiling of acetylation mediated by HAT1 in HepG2 cells. Interestingly‚ we identified a total of 858 Kac sites on 547 proteins in the HepG2 cell line‚ in which HAT1 mediated the levels of Kac of 74 sites on 68 proteins. The pathways and metabolic processes that were affected by HAT1-dependent acetylation modification were analyzed by bioinformatics. The results show that Kac regulates disease development‚ RNA biology‚ spliceosome and nucleosome assembly‚ oxidative stress‚ various signaling pathways and metabolic pathways‚ etc.. Moreover‚ we verified that the HAT1-mediated acetylation modification could promote abnormal lipid metabolism. CCK8 assays‚ clone formation and Edu assays revealed that HAT1 could remarkably enhance the cell proliferation of liver cancer in vitro. Thus‚ our finding explored the profiling of HAT1-mediated protein acetylation in HepG2 cells‚ which provides new insights into the underlying mechanism by which HAT1 mediates the development of liver cancer. Clinically‚ the HAT1-mediated acetylation sites could be used for the precise targets of drug development.
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Malaria is a deadly, infectious disease caused by the parasite Plasmodium, leading to millions of deathsworldwide. Plasmodium requires a coordinated pattern of sequential gene expression for surviving in bothinvertebrate and vertebrate host environments. As parasites largely depend on host resources, they also developefficient mechanisms to sense and adapt to variable nutrient conditions in the environment and modulate theirvirulence. Earlier we have shown that PfGCN5, a histone acetyltransferase, binds to the stress-responsive andvirulence-related genes in a poised state and regulates their expression under temperature and artemisinintreatment conditions in P. falciparum. In this study, we show upregulation of PfGCN5 upon nutrient stresscondition. With the help of chromatin immunoprecipitation coupled high-throughput sequencing (ChIP-seq)and transcriptomic (RNA-sequencing) analyses, we show that PfGCN5 is associated with the genes that areimportant for the maintenance of parasite cellular homeostasis upon nutrient stress condition. Furthermore, weidentified various metabolic enzymes as interacting partners of PfGCN5 by immunoprecipitation coupled withmass spectroscopy, possibly acting as a sensor of nutrient conditions in the environment. We also demonstratedthat PfGCN5 interacts and acetylates PfGAPDH in vitro. Collectively, our data provides important insights intotranscriptional deregulation upon nutrient stress condition and elucidate the role of PfGCN5 during nutrientstress condition.
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Objective To study the changes of acetyl-histone H2B in the cochlear hair cells of the guinea pig model of noise-induced hearing loss (NIHL).Methods Sixty guinea pigs were randomly divided into control and noise-exposure group.Thirty guinea pigs in the noise-exposure group were exposed to narrowband noise at 122 dB SPL for 3 hours , while thirty guinea pigs in the control group were not exposed to noise.Auditory thresholds were assessed by auditory brainstem response (ABR), prior to noise in two groups and 3, 7,14 and 21 days after noise exposure in the noise group.Then we investigated the expression of acetyl-histone H2B levels in the sensory cells of basilar membrane after noise expose by immunofluorescence staining and western blot.Results Compared with pre-exposure hearing, ABR thresholds were increased at 1h, 3, 7, 14 and 21 days after noise exposure, and recovered gradually with time and reached a permanent threshold shift at 14 days.The expression of acetyl-histone H2B was down-regulated in the hair cells and Hensen''s cells of the guinea pig cochlea after the noise expose , The ratio of H2B-AcK5 / β-actin was 0.6179±0.1260 in the control group and 0.3102±0.0839 in the noise group, and the difference was statistically significant (P<0.01).Conclusion Noise decreased the inner ear sensory cells histone acetylation level and histone acetylation imbalance may be involved in the occurrence of NIHL.
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Histone acetyltransferases(HATs) faciliate histone acetylation and histone deacetylases(HDACs) serve to remove acetyl groups from histones.The activation and repression of gene expression can be regulated by the acetylation of histone or specific genes.It is certified that acetylation of related genes is down-regulated in diabetic retinopathy,retinal ischemia-reperfusion,degenerative retinopathy,infective retinopathy and retinal tumors,which results in cell apoptosis and retinal dysfunction.So the physiology and pathology of retina have a close relation.The effects of histone acetylation and deacetylases on retinal diseases are still studying because of the complexity and diversity of genetic modification io epigenetic inheritance.This article reviewed the classification of HATs and HDACs and their inhibitors,their effects and function,their relationship to retinopathy,and discuss the protection of their inhibitors to retina.