β-arrestin1 is involved in hepatocellular carcinogenesis via an inflammation-mediated Akt signal
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ABSTRACT: Hepatocellular carcinoma (HCC), the main form of liver cancer, is the sixth most common cancer and the third most frequent cause of cancer death worldwide1. The exact mechanism of HCC initiation and development is still unclear, though inflammation has been shown to play a key role in this progression. Herein, we performed a gene expression assay to screen for alterative expression of genes among normal liver tissues, HCC tissues and its paracancer tissues with hepatitis. A gene assay to screen the expression of total RNA in liver tissues, including 3 normal liver tissues, 3 HCC paracancer specimens and 3 HCC samples with HBV-induced hepatitis. The normal liver samples were obtained from normal hepatic tissue in three hepatic hemangioma surgical operative patients, and three matched pairs of HCC and its paracancer tissues were respectively obtained from three HCC surgical operative patients without any chemotherapy and radiotherapy.
Project description:Hepatitis B virus (HBV) infection is one of the major causes of hepatocellular carcinoma (HCC). Nucleos(t)ide analogue (NA) therapy is effective to reduce the HCC incidence, while it doesn’t completely prevent HCC. In this study, we explored the involvement of microRNA (miRNA) in the post-NA treatment HCC development. Chronic hepatitis B (CHB) patients who received NA treatment (n = 18) were divided into 2 groups: those who didn’t develop HCC during the follow-up period (non-HCC group) and those who developed HCC after treatment (HCC group). Liver specimens were obtained before and after NA therapy, and HCC tissues were also obtained from the HCC group patients. Normal liver tissues were also obtained from 4 liver hemangioma patients who underwent surgical resection. miRNA expression was analyzed using Agilent miRNA microarray V3.
Project description:We applied small RNA Solexa sequencing technology to identify microRNA expression in human liver samples from surgically removed liver tissues including three normal liver tissues (distal normal liver tissue of liver hemangioma), an hepatitis B virus (HBV)-infected liver, a severe chronic hepatitis B liver, two HBV-related hepatocellular carcinoma (HCC), an hepatitis C virus (HCV)-related HCC, and an HCC without HBV or HCV infection. All samples were collected with the informed consent of the patients and the experiments were approved by the ethics committee of Second Military Medical University, Shanghai, China. We investigated the miRNome in human normal liver and suggested some deregulated abundantly expressed microRNAs in HCC. center_name: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China. Examination of miRNome in human liver samples from surgically removed liver tissues including three normal liver tissues (distal normal liver tissue of liver hemangioma), an hepatitis B virus (HBV)-infected liver tissue, a severe chronic hepatitis B liver tissue, an HBV-related hepatocellular carcinoma (HCC) tissue and adjacent liver tissues of different regions,an HBV-related HCC tissue and adjacent liver tissue, an hepatitis C virus (HCV)-related HCC tissue and adjacent liver tissue, and an HCC without HBV or HCV infection and adjacent liver tissue. All 15 human liver tissue samples.
Project description:Hepatocellular carcinoma (HCC), the main form of liver cancer, is the sixth most common cancer and the third most frequent cause of cancer death worldwide1. The exact mechanism of HCC initiation and development is still unclear, though inflammation has been shown to play a key role in this progression. Herein, we performed a gene expression assay to screen for alterative expression of genes among normal liver tissues, HCC tissues and its paracancer tissues with hepatitis.
Project description:We evaluated the expression of known human miRNAs in human hepatocellular carcinoma (HCC) and normal hepatic tissues from southeast China, and identified the differentially expressed miRNAs in HCC tissues. We use microRNA array platform from CapitalBio Corp. to access the miRNA expression profiles in HCC and non-tumor liver samples from Southeast China. There were 5 HCC samples and 3 non-tumor liver samples in our study. As the microarray platform we used was based on a older version of miRBase, we mapped the probe sequences to a newer version of miRBase before these data was applied to further analysis.
Project description:Saliva is rich in proteins, DNA, RNA and microorganisms, and can be regarded as a biomarker library. In order to explore a noninvasive and simple means of early screening for liver cancer, proteomics was used to screen salivary markers of hepatitis B associated liver cancer. We used mass spectrometry coupled isobaric tags for relative and absolute quantitation (iTRAQ)-technology to identify differentially expressed proteins (DEPs). Western blot, immunohistochemistry and enzyme linked immunosorbent assay were used to detect marker expression of in tissues and saliva. Statistical analysis was used to analyze the diagnostic efficacy of the markers was analyzed through statistical analyses. By comparing the hepatocellular carcinoma (HCC) group with non-HCC groups, we screened out 152 salivary DEPs. We found orosomucoid 1(ORM1) had significantly higher expression in saliva of HCC patients compared with non-HCC groups (p<0.001) and the expression of ORM1 in liver cancer tissues was significantly higher than that in adjacent normal tissues(p<0.001). The combination of salivary ORM1 and alpha-fetoprotein (AFP) showed reasonable specificities and sensitivities for detecting HCC. In a word, salivary ORM1 as a new biomarker of hepatitis B associated hepatocellular carcinoma, combination of salivary ORM1 and AFP as an improved diagnostic tool for hepatocellular carcinoma.
Project description:We applied small RNA Solexa sequencing technology to identify microRNA expression in human liver samples from surgically removed liver tissues including three normal liver tissues (distal normal liver tissue of liver hemangioma), an hepatitis B virus (HBV)-infected liver, a severe chronic hepatitis B liver, two HBV-related hepatocellular carcinoma (HCC), an hepatitis C virus (HCV)-related HCC, and an HCC without HBV or HCV infection. All samples were collected with the informed consent of the patients and the experiments were approved by the ethics committee of Second Military Medical University, Shanghai, China. We investigated the miRNome in human normal liver and suggested some deregulated abundantly expressed microRNAs in HCC. center_name: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China.
Project description:Hepatocellular carcinoma (HCC) is one of the most malignant and lethal cancers in the world. Its complex process of molecular pathogenesis indicates that HCC is caused by multiple etiological factors and involves multiple types of genes during its development and progression. In the current study, we performed a microarray analysis on the mRNA transcriptome of HCC (C), peri-cancerous liver (P) and normal liver (N) tissues. After integrating these results with information from the Gene Ontology and KEGG Pathway databases, we analyzed the potential interactions between different genes and constructed an interaction network, and identified the regulator, mediator and effector genes in this interaction network. Three types of tissues: 49 pairs of homogenous human primary hepatocellular carcinoma (Cancer, C) and pericancer liver tissues (Pericancer, P), 10 normal liver tissues (Normal, N). Three-condition experiment, HCC vs. Normal and Pericancer vs. Normal.
Project description:Background: Several studies have investigated the association of miRNAs with hepatocellular carcinoma (HCC) but the data are not univocal. Methods: We performed a microarray study of miRNAs in hepatitis C virus (HCV)-associated HCC and other liver diseases and healthy conditions. Results and Conclusions: The simultaneous comparison of different liver diseases and normal livers allowed the identification of 18 miRNAs exclusively expressed in HCV-associated HCC, with sensitivity and specificity values of diagnostic-grade. A total number of 76 liver specimens obtained from 43 patients were analyzed: 26 liver specimens obtained from 10 patients with HCV-associated HCC, including 9 specimens from the tumor area (HCC) and 17 specimens from the surrounding non-tumorous tissue affected by cirrhosis (HCC-CIR); 18 specimens from 10 patients with HCV-associated cirrhosis without HCC (CIR); 13 specimens from 4 patients with HBV-associated acute liver failure (ALF); 12 specimens from 12 liver donors (LD); and 7 from normal liver of 7 subjects who underwent hepatic resection for liver angioma (NL).
Project description:Twelve pairs of tumorous and peritumorous liver tissues (6 HBV- and 6 HCV-related HCC) that were obtained during the surgical liver resection of HCC patients were subjected to cDNA microarray analysis (Agilent Human Gene Expression v2 4x44K Microarray Kit) to screen the genes with expression levels that were different in the tumor than they were in the peritumorous tissue.
Project description:Hepatocellular carcinoma (HCC) is the second most common cause of cancer deaths worldwide. Altered DNA methylation landscapes are ubiquitous features of cancer. Interpretation of epigenetic aberrations in HCC is confounded by effects of multiple etiologic drivers and underlying cirrhosis in most cases. We globally profiled the DNA methylome of 34 normal livers and 122 primary liver disease tissues arising in the setting of chronic hepatitis B (HBV) or C (HCV) viral infection, alcoholism (EtOH), and other causes to examine how these environmental agents impact DNA methylation in a manner that contributes to liver disease. Our results demonstrate that each etiologic factor leaves unique and overlapping signatures on the DNA methylome. CpGs aberrantly methylated in cirrhosis-HCV and conserved in HCC were enriched for cancer driver genes, suggesting a pathogenic role for HCV-induced methylation changes. Additionally, large genomic regions displaying stepwise hypermethylation or hypomethylation during disease progression were identified. HCC-HCV/EtOH methylomes overlap highly with cryptogenic HCC, suggesting shared epigenetically deregulated pathways for hepatic carcinogenesis. Finally, overlapping methylation abnormalities between primary and cultured tumors unveil highly conserved epigenetic signatures in HCC. Taken together, this study characterizes progressive liver DNA methylome changes under exposure to detrimental environmental agents and illuminates possible biomarkers for early detection of HCC. 156 primary tissues and 25 cultured normal and HCC cell lines