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https://www.readbyqxmd.com/read/28105934/charm-discovery-of-combinatorial-chromatin-modification-patterns-in-hepatitis-b-virus-x-transformed-mouse-liver-cancer-using-association-rule-mining
#1
Sung Hee Park, Sun-Min Lee, Young-Joon Kim, Sangsoo Kim
BACKGROUND: Various chromatin modifications, identified in large-scale epigenomic analyses, are associated with distinct phenotypes of different cells and disease phases. To improve our understanding of these variations, many computational methods have been developed to discover novel sites and cell-specific chromatin modifications. Despite the availability of existing methods, there is still room for further improvement when they are applied to resolve the histone code hypothesis. Hence, we aim to investigate the development of a computational method to provide new insights into de novo combinatorial pattern discovery of chromatin modifications to characterize epigenetic variations in distinct phenotypes of different cells...
December 13, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/28103177/hbxip-a-binding-protein-of-hbx-regulates-maintenance-of-the-g2-m-phase-checkpoint-induced-by-dna-damage-and-enhances-sensitivity-to-doxorubicin-induced-cytotoxicity
#2
Hong-Rong Fei, Yun-Sheng Zhou, Ruo-Tong Li, Ming-Feng Yang, Jian Ma, Feng-Ze Wang
To maintain the integrity of the genome, cells need to detect and repair DNA damage before they complete cell division. Hepatitis B x-interacting protein (HBXIP), a binding protein of HBx (Hepatitis B virus x protein), is aberrantly overexpressed in human cancer cells and show to promote cell proliferation and inhibit apoptosis. The present study is designed to investigate the role of HBXIP on the DNA damage response. Our results show that HBXIP acts as an important regulator of G2/M checkpoint in response to DNA damage...
January 19, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28102846/hepatitis-b-virus-x-protein-promotes-the-stem-like-properties-of-ov6-cancer-cells-in-hepatocellular-carcinoma
#3
Chao Wang, Ming-da Wang, Peng Cheng, Hai Huang, Wei Dong, Wei-Wei Zhang, Peng-Peng Li, Chuan Lin, Ze-Ya Pan, Meng-Chao Wu, Wei-Ping Zhou
Hepatitis B virus X protein (HBx) and cancer stem-like cells (CSCs) have both been implicated in the occurrence and development of HBV-related hepatocellular carcinoma (HCC). However, whether HBx contributes to the stem-like properties of OV6(+) CSCs in HCC remains elusive. In this study, we showed that the concomitant expression of HBx and OV6 was closely associated with the clinical outcomes and prognosis of patients with HBV-related HCC. HBx was required for the stem-like properties of OV6(+) liver CSCs, including self-renewal, stem cell-associated gene expression, tumorigenicity and chemoresistance...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28102638/farnesoid-x-receptor-ablation-sensitizes-mice-to-hepatitis-b-virus-x-protein-induced-hepatocarcinogenesis
#4
Yongdong Niu, Meishu Xu, Betty L Slagle, Haihua Huang, Song Li, Grace L Guo, Ganggang Shi, Wenxin Qin, Wen Xie
: Chronic hepatitis B virus infection is a major risk factor for hepatocellular carcinoma (HCC). Hepatitis B virus X protein (HBx) is a hepatitis B virus protein that has multiple cellular functions, but its role in HCC pathogenesis has been controversial. Farnesoid X receptor (FXR) is a nuclear receptor with activities in anti-inflammation and inhibition of hepatocarcinogenesis. However, whether or how FXR can impact hepatitis B virus/HBx-induced hepatocarcinogenesis remains unclear...
November 5, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28098260/hepatitis-b-virus-x-protein-is-capable-of-down-regulating-protein-level-of-host-antiviral-protein-apobec3g
#5
Ruidong Chen, Xue Zhao, Yongxiang Wang, Youhua Xie, Jing Liu
The apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) family proteins bind RNA and single-stranded DNA, and create C-to-U base modifications through cytidine deaminase activity. APOBEC3G restricts human immunodeficiency virus 1 (HIV-1) infection by creating hypermutations in proviral DNA, while HIV-1-encoded vif protein antagonizes such restriction by targeting APOBEC3G for degradation. APOBEC3G also inhibits hepatitis B virus (HBV): APOBEC3G co-expression inhibits HBV replication and evidences exist indicating APOBEC3G-mediated HBV hypermutations in patients...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097530/virus-induced-hepatocellular-carcinoma-with-special-emphasis-on-hbv
#6
REVIEW
Ming Wang, Dong Xi, Qin Ning
Hepatocellular carcinoma (HCC) is a common malignant tumor with high lethality, and the hepatitis B virus (HBV) is a chief cause. HBV can accelerate HCC via multiple mechanisms. First, HBV induces immune reactions that lead to repeated hepatic inflammation, fibrosis and a deficient immune microenvironment. Subsequently, HBV can modify host genes near the insertion point through DNA integration to cause host cell genome instability and to generate carcinogenic fusion proteins. Additionally, HBV expresses diverse active proteins, especially HBx and HBs, which have a range of transactivation functions such as regulation of apoptosis, interference with intracellular signaling pathways, and alteration of epigenetics...
January 17, 2017: Hepatology International
https://www.readbyqxmd.com/read/28095508/the-smc5-6-complex-restricts-hbv-when-localized-to-nd10-without-inducing-an-innate-immune-response-and-is-counteracted-by-the-hbv-x-protein-shortly-after-infection
#7
Congrong Niu, Christine M Livingston, Li Li, Rudolf K Beran, Stephane Daffis, Dhivya Ramakrishnan, Dara Burdette, Leanne Peiser, Eduardo Salas, Hilario Ramos, Mei Yu, Guofeng Cheng, Michel Strubin, William E Delaney Iv, Simon P Fletcher
The structural maintenance of chromosome 5/6 complex (Smc5/6) is a restriction factor that represses hepatitis B virus (HBV) transcription. HBV counters this restriction by expressing HBV X protein (HBx), which targets Smc5/6 for degradation. However, the mechanism by which Smc5/6 suppresses HBV transcription and how HBx is initially expressed is not known. In this study we characterized viral kinetics and the host response during HBV infection of primary human hepatocytes (PHH) to address these unresolved questions...
2017: PloS One
https://www.readbyqxmd.com/read/28074857/deubiquitylation-of-hepatitis-b-virus-x-protein-hbx-by-ubiquitin-specific-peptidase-15-usp15-increases-hbx-stability-and-its-transactivation-activity
#8
Zhi-Jun Su, Jia-Shou Cao, Yan-Fang Wu, Wan-Nan Chen, Xinjian Lin, Yun-Li Wu, Xu Lin
Hepatitis B virus X protein (HBx) plays important roles in viral replication and the development of hepatocellular carcinoma. HBx is a rapid turnover protein and ubiquitin-proteasome pathway has been suggested to influence HBx stability as treatment with proteasome inhibitors increases the levels of HBx protein and causes accumulation of the polyubiquitinated forms of HBx. Deubiquitinases (DUBs) are known to act by removing ubiquitin moieties from proteins and thereby reverse their stability and/or activity...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28053323/hbx-promotes-cell-proliferation-by-disturbing-the-cross-talk-between-mir-181a-and-pten
#9
Yi Tian, Xinqiang Xiao, Xing Gong, Feng Peng, Yun Xu, Yongfang Jiang, Guozhong Gong
Hepatitis B virus X protein (HBx) is involved in the initiation and progression of hepatocellular carcinoma (HCC). However, the mechanism is still needed to be elucidated. In this study, we explored the relationship between HBx and microRNA and their roles in hepato-carcinogenesis. Firstly, by global microarray-based microRNA profiling and qRT-PCR, we found miR-181a was strongly up-regulated in HepG2.2.15 cells (HBV positive) and pHBV1.3-expressing HepG2 cells, and HBx played a major role in it. Secondly, reduced PTEN protein expression in the presence of HBx was aslo mediated by miR-181a, and in the Luciferase reporter system, miR-181a inhibited the PTEN translation by binding the PTEN 3'-untranslated-region (UTR), and PTEN protein was decreased when epigenetic expression of miR-181a and rescued by knocking down miR-181a...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27975314/measuring-changes-in-cytosolic-calcium-levels-in-hbv-and-hbx-expressing-cultured-primary-hepatocytes
#10
Jessica C Casciano, Michael J Bouchard
Chronic infection with hepatitis B virus (HBV) remains a major worldwide health concern and is the leading cause of hepatocellular carcinoma (HCC). The HBV X protein (HBx) is the only regulatory protein encoded in the HBV genome; HBx stimulates HBV replication in vivo and in vitro. HBx also regulates cytosolic Ca(2+) signaling, and altered Ca(2+) signaling is associated with the development of many diseases, including HCC. Importantly, many HBx functions, including HBx modulation of cell proliferation, apoptosis, and transcription pathways, have been linked to changes in cytosolic Ca(2+) signaling...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27925189/hbx-drives-alpha-fetoprotein-expression-to-promote-initiation-of-liver-cancer-stem-cells-through-activating-pi3k-akt-signal-pathway
#11
Mingyue Zhu, Wei Li, Yan Lu, Xu Dong, Bo Lin, Yi Chen, Xueer Zhang, Junli Guo, Mengsen Li
Hepatitis B virus (HBV)-X protein (HBx) plays critical role in inducing the malignant transformation of liver cells. Alpha fetoprotein (AFP) expression is closely related to hepatocarcinogenesis. We report that Oct4, Klf4, Sox2 and c-myc expression positively associated with AFP(+)/HBV(+) hepatocellular carcinoma(HCC) tissues, and the expression of the stemness markers CD44, CD133 and EpCAM was significantly higher in AFP(+)/HBV(+) HCC tissues compared to normal liver tissues or AFP(-)/HBV(-) HCC tissues. AFP expression turned on prior to expression of Oct4, Klf4, Sox2 and c-myc, and the stemness markers CD44, CD133 and EpCAM in the normal human liver L-02 cell line or CHL cell lines upon transfection with MCV-HBx vectors...
December 7, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27920474/hepatitis-b-virus-upregulates-host-expression-of-%C3%AE-1-2-mannosidases-via-the-ppar%C3%AE-pathway
#12
Song Hu, Li-Bin Jiang, Xiao-Jing Zou, Wei Yi, De-Ying Tian
AIM: To assess the effects of hepatitis B virus (HBV) on the expression of host α-1,2-mannosidases and determine the underlying mechanisms. METHODS: We measured the expression levels of MAN1A1, MAN1A2, MAN1B1, and MAN1C1 in cell lines HepG2.2.15, HepN10, HepAD38 and HepG2 by Western blot. Viral antigens (HBsAg and HBeAg) in the culture medium were measured using the chemiluminescence method. HBV DNA quantification assays were performed using a commercial real-time PCR kit...
November 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27909336/c-terminal-truncated-hbv-x-promotes-hepato-oncogenesis-through-inhibition-of-tumor-suppressive-%C3%AE-catenin-bambi-signaling
#13
Seok Lee, Mi-Jin Lee, Jun Zhang, Goung-Ran Yu, Dae-Ghon Kim
C-terminal-truncated hepatitis B virus (HBV) X (HBx) (ctHBX) is frequently detected in hepatocellular carcinoma (HCC) through HBV integration into the host genome. However, the molecular mechanisms underlying ctHBx-associated oncogenic signaling have not yet been clarified. To elucidate the biological role of ctHBx in hepato-oncogenesis, we functionally analyzed ctHBx-mediated regulation of the activin membrane-bound inhibitor bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) through transforming growth factor-β (TGF-β) or β-catenin (CTNNB1) in HCC cells and in an animal model, and we compared its role to that of the full-length HBx protein...
December 2, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27902472/molecular-mechanism-of-hepatitis-b-virus-hbv-on-suppression-of-raf-kinase-inhibitor-protein-rkip-expression
#14
Xiao-Ke Cheng, Guo-Zheng Yu, Xiao-Dong Li, Xue-Qun Ren
Raf kinase inhibitor protein (RKIP) has been shown to be a suppressor of the mitogen-activated protein kinase pathway and is reported to be involved in human malignancy. However, the molecular mechanism of hepatitis B virus (HBV) in regulating RKIP expression is not yet clarified. In this study, we compared RKIP expression in 107 pairs of matched liver cancer and adjacent non-cancerous liver tissues. Among seven HBV-encoded proteins, we found HBV X (HBX) protein could significantly inhibit the expression level of RKIP, indicating that HBV could suppress RKIP expression through regulating HBX...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27883059/hepatic-satb1-induces-paracrine-activation-of-hepatic-stellate-cells-and-is-upregulated-by-hbx
#15
Jin Gong, Wei Tu, Jian Han, Jiayi He, Jingmei Liu, Ping Han, Yunwu Wang, Mengke Li, Mei Liu, Jiazhi Liao, Dean Tian
Chronic hepatitis B virus (HBV) infection is a major cause of chronic liver diseases, but its involvement in hepatic fibrogenesis remains unclear. Special AT-rich binding protein 1 (SATB1) has been implicated in reprogramming chromatin organization and transcription profiles in many cancers and non-cancer-related conditions. We found that hepatic SATB1 expression was significantly up-regulated in fibrotic tissues from chronic hepatitis B virus (HBV)-infected patients and HBV transgenic (HBV-Tg) mouse model...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27880978/defining-the-relationship-between-farsenoid-x-receptor-hepatitis-b-virus-x-protein-and-hcc-it-s-complicated
#16
EDITORIAL
Lindsey Kennedy, Heather Francis
The relationship between hepatitis B virus X protein (HBx), farsenoid X receptor (FXR) and hepatocellular carcinoma (HCC) is a complicated one in that we have a viral protein interaction that can drive tumorigenesis or inhibit HCC depending upon transactivation of full-length or truncated HBx. In the current article the authors have elegantly described a system of HBx-FXR interaction that demonstrates inhibition of HCC tumor growth via activation of full-length HBx. The paper employs both in vivo and in vitro studies including using FXR knockout mice crossed with HBx induced mice...
November 23, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27864147/host-factor-prpf31-is-involved-in-cccdna-production-in-hbv-replicating-cells
#17
Wataru Kinoshita, Naoki Ogura, Koichi Watashi, Takaji Wakita
Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) plays a central role in chronic HBV infection and replication, and is an important factor for HBV surface antigen loss indicating the endpoint of HBV treatment. However, there is a known problem that current anti-HBV drugs, including interferons and nucleos(t)ide analogues, reduce HBV replication but have a little or no effect on reducing cccDNA. Therefore, the development of new therapeutic agents is necessary to eradicate cccDNA. In this study, we identified pre-mRNA processing factor 31 (PRPF31) by siRNA screening as a factor associated with cccDNA...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27821177/hepatitis-b-virus-x-protein-promotes-interleukin-7-receptor-expression-via-nf-%C3%AE%C2%BAb-and-notch1-pathway-to-facilitate-proliferation-and-migration-of-hepatitis-b-virus-related-hepatoma-cells
#18
Fanyun Kong, Wei Hu, Kai Zhou, Xiao Wei, Yanbo Kou, Hongjuan You, Kuiyang Zheng, Renxian Tang
BACKGROUND: Interleukin-7 receptor (IL-7R) is involved in the abnormal function of solid tumors, but the role and regulatory mechanisms of IL-7R in HBV-related hepatocellular carcinoma (HCC) are still unclear. METHODS: Gene and protein expression levels of IL-7R were examined in hepatoma cells transfected with hepatitis B virus (HBV) plasmids and in hepatoma cells transfected with the multifunctional nonstructural protein X (HBX). The expression of HBX and IL-7R was measured by immunohistochemical analysis in HBV-related HCC tissues...
November 7, 2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27819342/minicircle-hbv-cccdna-with-a-gaussia-luciferase-reporter-for-investigating-hbv-cccdna-biology-and-developing-cccdna-targeting-drugs
#19
Feng Li, Liang Cheng, Christopher M Murphy, Natalia J Reszka-Blanco, Yaxu Wu, Liqun Chi, Jianming Hu, Lishan Su
Chronic Hepatitis B Virus (HBV) infection is generally not curable with current anti-viral drugs. Virus rebounds after stopping treatment from the stable HBV covalently-closed-circular DNA (cccDNA). The development of drugs that directly target cccDNA is hampered by the lack of robust HBV cccDNA models. We report here a novel HBV cccDNA technology that will meet the need. We engineered a minicircle HBV cccDNA with a Gaussia Luciferase reporter (mcHBV-GLuc cccDNA), which serves as a surrogate to measure cccDNA activity...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27798869/ursolic-acid-suppresses-hepatitis-b-virus-x-protein-mediated-autophagy-and-chemotherapeutic-drug-resistance
#20
Ching-Dong Chang, Ping-Yuan Lin, Jue-Liang Hsu, Wen-Ling Shih
Hepatitis B virus X (HBx) protein is a multifunctional oncoprotein that affects diverse cell activities via regulation of various host cell signaling pathways. The current investigation demonstrated that ursolic acid (UA), a pentacyclic triterpenoid, protected hepatoma cells and reduced HBx-mediated autophagy through modulation of Ras homolog gene family member A (RhoA). Low-level ectopic HBx expression in Huh7 cells induced more significant autophagosome formation than high-level HBx expression. HBx activated beclin-1 promoter and enhanced the beclin-1 protein expression under low HBx expression...
2016: Anticancer Research
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