Inhibition of the Cell Death Pathway in Nonalcoholic Steatohepatitis (NASH)-Related Hepatocarcinogenesis Is Associated with Histone H4 lysine 16 Deacetylation

Hepatocellular carcinoma (HCC) is one of the most aggressive human cancers, and its incidence is steadily increasing worldwide. Recent epidemiologic findings have suggested that the increased incidence of HCC is associated with obesity, type II diabetes mellitus, and nonalcoholic steatohepatitis (NASH); however, the mechanisms and the molecular pathogenesis of NASH-related HCC are not fully understood. To elucidate the underlying mechanisms of the development of NASH-related HCC, we investigated the hepatic transcriptomic and histone modification profiles in Stelic Animal Model mice, the first animal model of NASH-related HCC to resemble the disease pathogenesis in humans. The results demonstrate that the development of NASH-related HCC is characterized by progressive transcriptomic alterations, global loss of histone H4 lysine 20 trimethylation (H4K20me3), and global and gene-specific deacetylation of histone H4 lysine 16 (H4K16). Pathway analysis of the entire set of differentially expressed genes indicated that the inhibition of cell death pathway was the most prominent alteration, and this was facilitated by persistent gene-specific histone H4K16 deacetylation. Mechanistically, deacetylation of histone H4K16 was associated with downregulation of lysine acetyltransferase KAT8, which was driven by overexpression of its inhibitor nuclear protein 1 (Nupr1). The results of this study identified a reduction of global and gene-specific histone H4K16 acetylation as a key pathophy...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Chromatin, Epigenetics, and RNA Regulation Source Type: research

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We present a narrative review of HCC in Africa, discussing present and future trends. [...] Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.Article in Thieme eJournals: Table of contents  |  Abstract  |  Full text
Source: Seminars in Liver Disease - Category: Gastroenterology Authors: Tags: Review Article Source Type: research
Abstract BACKGROUND: Postoperative complications have a great impact on the postoperative course and oncological outcomes following major cancer surgery. Among them, infective complications play an important role. The aim of this study was to evaluate whether postoperative infective complications influence long-term survival after liver resection for hepatocellular carcinoma (HCC). METHODS: Patients who underwent resection with curative intent for HCC between July 2003 and June 2016 were identified from a multicentre database (8 institutions) and analysed retrospectively. Independent risk factors for postoper...
Source: The British Journal of Surgery - Category: Surgery Authors: Tags: Br J Surg Source Type: research
Conclusion: 3T3-L1 cells, treated with LPV/RTV, show altered lipid content due to increased miRNA-218 levels, which affects lipin-1 mRNA. Moreover, increased miRNA-218 levels were inversely correlated with changes in GLUT-4 expression, which suggests a role for miRNA-218 in mediating the insulin resistance consequent to cART. Introduction Metabolic syndrome is a serious consequence of combined Antiretroviral Therapy (cART). HIV-associated metabolic syndrome is often accompanied by lipodystrophy (LS), the redistribution of body fat with loss of subcutaneous adipose tissue in face, limbs and buttocks, concomitant wit...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Dan Hu1†, Meijin Zhang2†, Hejun Zhang1, Yan Xia1, Jinxiu Lin2, Xiongwei Zheng1, Feng Peng2* and Wenquan Niu3* 1Department of Pathology, Fujian Cancer Hospital &Fujian Medical University Cancer Hospital, Fuzhou, China 2Department of Cardiology, First Affiliated Hospital of Fujian Medical University, Fuzhou, China 3Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China Background and Objectives: Growing evidence indicates that metabolic syndrome confers a differential risk for the development and progression of many types of cancer, especially in the digestive tr...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusion As a critical regulator of inflammation and cell survival, the NFκB pathway is a promising target for diagnosing and treating kidney diseases. For modulation of the NFκB pathway in the clinic, a number of molecules can effectively inhibit NFκB signaling by targeting the receptors, associated adaptors, IKKs, IκBs and transcriptional regulators (144). There is further clinical evidence on small-molecule inhibitors of IKKα and NIK from recent trials on anti-cancer therapies (145). These clinical trials showed that the cancer-selective pharmacodynamic response of DTP3, the co-inhibitor...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion Most head and neck pathologies show a broad cellular heterogeneity making it difficult to achieve an accurate diagnosis and efficient treatment (Graf and Zavodszky, 2017; Lo Nigro et al., 2017). Single cell analysis of circadian omics (Lande-Diner et al., 2015; Abraham et al., 2018), may be a crucial tool needed in the future to fully understand the circadian control of head and neck diseases. It becomes more obvious that there is only a small genetic component but a largely unknown epigenetics and/or environmental component for most of the head and neck pathologies (Moosavi and Motevalizadeh Ardekani, 2016; He...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Conclusions: Bariatric surgery appears to be capable of partially reversing the obesity-related epigenome. The identification of potential epigenetic biomarkers predictive for the success of bariatric surgery may open new doors to personalized therapy for severe obesity. Introduction Obesity is currently a huge healthcare problem, worldwide, and is a risk factor for several diseases such as type 2 diabetes (T2D), cardiovascular disease and cancer (1). As the prevalence of obesity reaches pandemic proportions, this metabolic disease is estimated to become the biggest cause of mortality in the near future (2). In fact,...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
Conclusion The expression of the components of the PTN-MK-RPTPβ/ζ axis in immune cells and in inflammatory diseases suggests important roles for this axis in inflammation. Pleiotrophin has been recently identified as a limiting factor of metainflammation, a chronic pathological state that contributes to neuroinflammation and neurodegeneration. Pleiotrophin also seems to potentiate acute neuroinflammation independently of the inflammatory stimulus while MK seems to play different -even opposite- roles in acute neuroinflammation depending on the stimulus. Which are the functions of MK and PTN in chronic neuroinfla...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
This study aimed to analyze the association of DNA methylation signatures at HCC pathway genes with obesity and related metabolic disturbances. A population of 474 adults within the Methyl Epigenome Network Association (MENA) project was included. DNA methylation levels were measured in white blood cells by microarray. The identification and discrimination of HCC pathway genes were performed using KEGG and PathDIP databases. Anthropometry measurements, the blood metabolic profile, and clinical data were analyzed. The methylation patterns of 20 CpG sites at HCC pathway genes strongly correlated with BMI (FDR
Source: Nutrition and Cancer - Category: Cancer & Oncology Authors: Tags: Nutr Cancer Source Type: research
Authors: Lau JKC, Zhang X, Yu J Abstract Non-alcoholic fatty liver disease (NAFLD) is a spectrum of diseases, which include simple liver steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). It is a burgeoning health problem worldwide in line with the trend towards unhealthy diet and increased prevalence of obesity and type 2 diabetes mellitus (T2DM). Many animal models that illustrate both the histology and pathology of human NAFLD have been established. It is important to choose an animal model that best conforms to the aim of the study. This chapter presents a critical an...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
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