showing 6 related works from this author
Induction of cancer cell stemness by depletion of macrohistone H2A1 in hepatocellular carcinoma.
2017
Hepatocellular carcinomas (HCC) contain a subpopulation of cancer stem cells (CSCs), which exhibit stem cellâlike features and are responsible for tumor relapse, metastasis, and chemoresistance. The development of effective treatments for HCC will depend on a molecular-level understanding of the specific pathways driving CSC emergence and stemness. MacroH2A1 is a variant of the histone H2A and an epigenetic regulator of stem-cell function, where it promotes differentiation and, conversely, acts as a barrier to somatic-cell reprogramming. Here, we focused on the role played by the histone variant macroH2A1 as a potential epigenetic factor promoting CSC differentiation. In human HCC section…
DNA Hypomethylation and Histone Variant macroH2A1 Synergistically Attenuate Chemotherapy-Induced Senescence to Promote Hepatocellular Carcinoma Progr…
2016
Abstract Aging is a major risk factor for progression of liver diseases to hepatocellular carcinoma (HCC). Cellular senescence contributes to age-related tissue dysfunction, but the epigenetic basis underlying drug-induced senescence remains unclear. macroH2A1, a variant of histone H2A, is a marker of senescence-associated heterochromatic foci that synergizes with DNA methylation to silence tumor-suppressor genes in human fibroblasts. In this study, we investigated the relationship between macroH2A1 splice variants, macroH2A1.1 and macroH2A1.2, and liver carcinogenesis. We found that protein levels of both macroH2A1 isoforms were increased in the livers of very elderly rodents and humans, a…
The association of variants in PNPLA3 and GRP78 and the risk of developing hepatocellular carcinoma in an Italian population
2016
// Daniele Balasus 1, * , Michael Way 2, * , Caterina Fusilli 3 , Tommaso Mazza 3 , Marsha Y. Morgan 2 , Melchiorre Cervello 4 , Lydia Giannitrapani 1 , Maurizio Soresi 1 , Rosalia Agliastro 5 , Manlio Vinciguerra 2, 6 , Giuseppe Montalto 1, 4 1 Biomedical Department of Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy 2 Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, London, UK 3 IRCCS Casa Sollievo della Sofferenza, Bioinformatics Unit, San Giovanni Rotondo (FG), Italy 4 Institute of Biomedicine and Molecular Immunology, National Research Council (C.N.R.), Palermo, Italy 5 Immunohematology and Trans…
Two single nucleotide polymorphisms in the MICA gene and sMICA plasma levels are associated with hepatocellular carcinoma development in an Italian p…
2017
Background & Aims: We investigated the relationships between MICA polymorphisms, sMICA levels and hepatocellular carcinoma (HCC) risk in HCC patients with chronic hepatitis C virus (HCV) infection. Methods.154 HCV-related HCC cases, 93 HCV-related liver cirrhosis (LC) cases and 244 healthy controls were genotyped using KASPTM SNP method. Levels of plasma soluble MICA (sMICA) were measured in 132 HCC, 90 LC patients and in 78 controls. Results. Genotyping of MICA rs2596542 showed that G/G genotype was significantly more frequent in HCC than in controls and in HCC than in LC patients. As for MICA rs2596538 allele C and C/C genotype were significantly more frequent in HCC than in controls …
Association between MICA Gene Variants and the Risk of Hepatitis C Virus-Induced Hepatocellular Cancer in a Sicilian Population Sample
2018
There are currently no biomarkers that predict hepatocellular carcinoma (HCC) risk in patients with hepatitis C virus (HCV)-related cirrhosis. We investigated the relationships among major histocompatibility complex (MHC) class I chain-related gene A (MICA) polymorphisms, plasma levels of soluble MICA (sMICA), and HCC risk in patients with HCV-related HCC. One hundred fifty-four HCV-related HCC patients, 93 HCV-related liver cirrhosis (LC) cases, and 244 healthy controls, all sampled from the native Sicilian population, were genotyped using the KASP™ single-nucleotide polymorphism genotyping method. The MICA rs2596542 polymorphism showed that the G/G genotype was significantly more frequent…
Histone Variant MacroH2A1 Marks Liver Aging and Orchestrates the Escape from Senescence Induced by DNA Hypomethylation in Hepatocellular Carcinoma
2015
The epigenetic basis of age-associated progression of liver diseases towards hepatocellular carcinoma (HCC) is unclear. MacroH2A1 is a variant of histone H2A1, present in the two isoforms, with fundamental roles in cell homeostasis. MacroH2A1 is a marker of senescence associated heterochromatic foci (SAHF) and synergizes with DNA demethylating chemotherapic agent 5-aza-2'-deoxycytidine (5-aza-dC) in silencing tumor suppressor genes in human fibroblasts. We show that protein levels of macroH2A1 isoforms are increased in the livers of old rodents and humans, and in human HCC tissue. Human HCC cells overexpressing macroH2A1 escape a 5-aza-dC-induced senescent phenotype, as determined by cell p…