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Xu Shi, Ying Tang, Xiguang Sun, Yufei Liu, Ying Sun, Munan Sun, Yanfang Jiang, Yulin Li
The current study aimed to investigate the distribution of memory and naïve T cell (TN) subsets in hepatitis B virus (HBV)‑infected patients at different immune stages and investigate the effect of interleukin 33 (IL‑33) on the regulation of the T‑cell subsets. The distributions of memory and naïve T cells were detected by flow cytometry. ELISA was conducted to assess the levels of IL‑4, IL‑5, IL‑10, IL‑12, interferon γ and tumor necrosis factor α. The expression levels of IL‑33 and HBV x protein (HBx) were measured by reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively...
October 13, 2016: Molecular Medicine Reports
Gu-Choul Shin, Hong Seok Kang, Ah Ram Lee, Kyun-Hwan Kim
Death receptors of TNFSF10/TRAIL (tumor necrosis factor superfamily member 10) contribute to immune surveillance against virus-infected or transformed cells by promoting apoptosis. Many viruses evade antiviral immunity by modulating TNFSF10 receptor signaling, leading to persistent infection. Here, we report that hepatitis B virus (HBV) X protein (HBx) restricts TNFSF10 receptor signaling via macroautophagy/autophagy-mediated degradation of TNFRSF10B/DR5, a TNFSF10 death receptor, and thus permits survival of virus-infected cells...
October 14, 2016: Autophagy
Hong Peng, Yongguo Li, Yunzhi Liu, Jingnan Zhang, Ke Chen, Ailong Huang, Hua Tang
Numerous evidences suggested that the hepatitis B virus (HBV) was recognized as an important factor in the development of hepatocellular carcinoma (HCC). Dickkopf-1 (DKK1) recently was reported to be involved in the progress of HCC. HBV may regulate DKK1 expression in hematoma carcinogenesis. Here, we demonstrated that HBV could regulate DKK1 promoter activity which resulted in upregulation of its mRNA and protein expression in several HBV existing cell lines, and HBx played a prominent role in this process...
October 10, 2016: Acta Biochimica Polonica
Kishor Pant, Ajay K Yadav, Parul Gupta, Abhishek Singh Rathore, Baibaswata Nayak, Senthil K Venugopal
Hepatitis B Virus (HBV) utilizes several mechanisms to survive in the host cells and one of the main pathways being autophagosome formation. Humic acid (HA), one of the major components of Mineral pitch, is an Ayurvedic medicinal food, commonly used by the people of the Himalayan regions of Nepal and India for various body ailments. We hypothesized that HA could induce cell death and inhibit HBV-induced autophagy in hepatic cells. Incubation of Hep G2.2.1.5 cells (HepG2 cells stably expressing HBV) with HA (100 μM) inhibited both cell proliferation and autophagosome formation significantly, while apoptosis induction was enhanced...
October 6, 2016: Scientific Reports
Zhongwei Xu, Linghui Zhai, Tailong Yi, Huiying Gao, Fengxu Fan, Yanchang Li, Youliang Wang, Ning Li, Xiaohua Xing, Na Su, Feilin Wu, Lei Chang, Xiuli Chen, Erhei Dai, Chao Zhao, Xiao Yang, Chunping Cui, Ping Xu
Hepatitis B virus X protein (HBx) participates in the occurrence and development processes of hepatocellular carcinoma (HCC) as a multifunctional regulation factor. However, the underlying molecular mechanism remains obscure. Here, we describe the use of p21HBx/+ mouse and SILAM (Stable Isotope Labeling in Mammals) strategy to define the pathological mechanisms for the occurrence and development of HBx induced liver cancer. We systematically compared a series of proteome samples from regular mice, 12- and 24-month old p21HBx/+ mice representing the inflammation and HCC stages of liver disease respectively and their nontransgenic wild-type (WT) littermates...
September 30, 2016: Oncotarget
Wei-Hsiang Lin, Shiou-Hwei Yeh, Kun-Huei Yeh, Kai-Wei Chen, Ya-Wen Cheng, Tung-Hung Su, Ping Jao, Lin-Chun Ni, Pei-Jer Chen, Ding-Shinn Chen
Transarterial chemoembolization (TACE) is the main treatment for intermediate stage hepatocellular carcinoma (HCC) with Barcelona Clinic Liver Cancer classification because of its exclusive arterial blood supply. Although TACE achieves substantial necrosis of the tumor, complete tumor necrosis is uncommon, and the residual tumor generally rapidly recurs. We combined tirapazamine (TPZ), a hypoxia-activated cytotoxic agent, with hepatic artery ligation (HAL), which recapitulates transarterial embolization in mouse models, to enhance the efficacy of TACE...
October 4, 2016: Proceedings of the National Academy of Sciences of the United States of America
Vishnu Prasad Adhikari, Lin-Jie Lu, Ling-Quan Kong
Lifestyle and family history are two of the most important risk factors for breast cancer (BC). However, these risk factors cannot explain the differences in the incidence and early BC onset among Chinese females compared to their western counterparts. We propose in this hypothesis the potential mechanism of indirect oncogenesis of hepatitis B virus (HBV) in causing BC through its persistence as occult infection and continuous replication with long term subtle liver damage. Estrogen is mainly deactivated in the liver and long term necro-inflammatory damage to liver may result in persistent high level of estrogen, which is a dominant risk factor for BC...
September 12, 2016: Chinese Clinical Oncology
Mahua Sinha, Clementina Rama Rao, C S Premalata, Mohammed Shafiulla, K C Lakshmaiah, Linu Abraham Jacob, Govind K Babu, B K Viveka, L Appaji, Jayshree R Subramanyam
CONTEXT: There is a need to study potential infective etiologies in lymphomas. Lymphocyte-transforming viruses can directly infect lymphocytes, disrupt normal cell functions, and promote cell division. Epstein-Barr virus (EBV) is known to be associated with several lymphomas, especially Hodgkin lymphomas (HLs). And recently, the lymphocyte-transforming role of hepatitis B virus (HBV) has been emphasized. AIMS: The aim of this study was to elucidate the association of two potentially oncogenic, widely prevalent latent DNA viruses, EBV and HBV, in non-HL (NHL)...
July 2016: Indian Journal of Medical and Paediatric Oncology
Chuck C K Chao
Hepatitis B virus X protein (HBx) plays an important role in the development of hepatocellular carcinoma (HCC). In addition, hepatoma upregulated protein (HURP) is a cellular oncogene that is upregulated in a majority of HCC cases. We highlight here recent findings demonstrating a link between HBx, HURP and anti-apoptosis effects observed in cisplatin-treated HCC cells. We observed that Hep3B cells overexpressing HBx display increased HURP mRNA and protein levels, and show resistance to cisplatin-induced apoptosis...
September 8, 2016: World Journal of Hepatology
Sha Fu, Rong-Rong Zhou, Ning Li, Yan Huang, Xue-Gong Fan
Encoded by the hepatitis B virus, hepatitis B virus X protein (HBx) is a multifunctional, potentially oncogenic protein that acts primarily during the progression from chronic hepatitis B to cirrhosis and hepatocellular carcinoma (HCC). In recent decades, it has been established that chronic inflammation generates a tumor-supporting microenvironment. HCC is a typical chronic inflammation-related cancer, and inflammation is the main risk factor for HCC progression. The viral transactivator HBx plays a pivotal role in the initiation and maintenance of hepatic inflammatory processes through interactions with components of the tumor microenvironment including tumor cells and the surrounding peritumoral stroma...
September 23, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Yu Qian, Boshi Wang, Aihui Ma, Li Zhang, Guiqin Xu, Qi Ding, Tiantian Jing, Lin Wu, Yun Liu, Zhaojuan Yang, Yongzhong Liu
Hepatitis B virus (HBV) infection is a major factor that contributes to the development of hepatocellular carcinoma (HCC). HBV X protein (HBx) has been shown to accelerate HCC progression by promoting tumour growth and metastasis. In the clinic, carboxyl-terminal truncated HBx (Ct-HBx) proteins are frequently present in HCC tumour tissues, but not in non-tumorous tissues. In this study, we analysed deubiquitinase expression profiles in cells with or without ectopic expression of the Ct-HBx proteins and observed that the expression of ubiquitin specific peptidase 16 (USP16) was substantially inhibited by Ct-HBx proteins...
2016: Scientific Reports
Christopher M Murphy, Yanping Xu, Feng Li, Kouki Nio, Natalia Reszka-Blanco, Xiaodong Li, Yaxu Wu, Yanbao Yu, Yue Xiong, Lishan Su
The hepatitis B virus (HBV) regulatory protein X (HBx) activates gene expression from the HBV covalently closed circular DNA (cccDNA) genome. Interaction of HBx with the DDB1-CUL4-ROC1 (CRL4) E3 ligase is critical for this function. Using substrate-trapping proteomics, we identified the structural maintenance of chromosomes (SMC) complex proteins SMC5 and SMC6 as CRL4(HBx) substrates. HBx expression and HBV infection degraded the SMC5/6 complex in human hepatocytes in vitro and in humanized mice in vivo. HBx targets SMC5/6 for ubiquitylation by the CRL4(HBx) E3 ligase and subsequent degradation by the proteasome...
September 13, 2016: Cell Reports
Ping He, Beiru Zhang, Dajun Liu, Xiaohui Bian, Detian Li, Yanqiu Wang, Guangping Sun, Guangyu Zhou
BACKGROUND/AIMS: The hepatitis B virus X protein (HBx) contributes to HBV-induced injury of renal tubular cells and induces apoptosis via Fas/FasL up-regulation. However, the mechanism of Fas/FasL activation is unknown. Recent studies indicated that HBx induction of apoptosis in hepatic cells depends on activating the MLK3-MKK7-JNKs signaling module, which then up-regulates FasL expression. In this study, we used NRK-52E cells transfected an HBx expression vector to examine the role of the MLK3-MKK7-JNKs signaling pathway on HBx-induced renal tubular cell injury...
2016: Cellular Physiology and Biochemistry
Yuzhuo Wu, Junhe Zhang, Huaihong Zhang, Yufeng Zhai
Hepatitis B virus (HBV) X protein (HBx) is implicated in the development of hepatocellular carcinoma (HCC). Yes-associated protein 1 (YAP) is an important proto-oncogene, which is a downstream effector molecule in the Hippo signaling pathway. The aim of the present study was to investigate the association between HBx expression in HCC samples and YAP expression in the Hippo pathway. A total of 20 pathologically confirmed HCC samples, 20 corresponding adjacent non-tumor liver tissues and 5 normal liver tissue samples were collected...
September 2016: Oncology Letters
Dian Yin, Yilang Wang, Wenli Sai, Liang Zhang, Yajun Miao, Lili Cao, Xiaolu Zhai, Xiu Feng, Li Yang
Hepatitis B virus (HBV) X protein (HBx) plays a key role in the initiation and progression of HBV infection‑induced hepatocellular carcinoma (HCC). Oncogenic microRNA-21 (miR-21) can be modulated by HBx protein in HCC. However, critical regulator genes in the pathway of HBx-induced miR-21 in HCC remain unclear. This study aimed to investigate the role of HBx-induced miR-21 in the apoptosis of HCC cells. In the study, interleukin-12 (IL-12) was demonstrated as a direct target of miR-21 by dual‑luciferase report assay, and miR-21 was highly expressed in HCC cells (HepG2 and HepG2 2...
October 2016: Oncology Reports
Marie-Pier Tremblay, Victoria E S Armero, Andréa Allaire, Simon Boudreault, Camille Martenon-Brodeur, Mathieu Durand, Elvy Lapointe, Philippe Thibault, Maude Tremblay-Létourneau, Jean-Pierre Perreault, Michelle S Scott, Martin Bisaillon
BACKGROUND: Dysregulations in alternative splicing (AS) patterns have been associated with many human diseases including cancer. In the present study, alterations to the global RNA splicing landscape of cellular genes were investigated in a large-scale screen from 377 liver tissue samples using high-throughput RNA sequencing data. RESULTS: Our study identifies modifications in the AS patterns of transcripts encoded by more than 2500 genes such as tumor suppressor genes, transcription factors, and kinases...
2016: BMC Genomics
Chaoyang Chen, Haodi Jia, Fei Zhang, Yanli Qin, Li Zong, Quan Yuan, Yongxiang Wang, Ningshao Xia, Jisu Li, Yumei Wen, Shuping Tong
Hepatitis B virus (HBV) has a 3.2-kb circular DNA genome. It employs four promoters in conjunction with a single polyadenylation signal to generate 3.5-, 2.4-, 2.1-, and 0.7-kb co-terminal RNAs. The 3.5-kb RNA is subdivided into the precore RNA for e antigen expression and pregenomic RNA for genome replication. When introduced to a genotype A clone, several core promoter mutations markedly enhanced HBV genome replication but suppressed e antigen expression through up regulation of pregenomic RNA at the expense of precore RNA...
August 23, 2016: Journal of General Virology
Woohyun Kim, Sooyoung Lee, Yeongnam Son, Chunkyu Ko, Wang-Shick Ryu
: HBx, a small regulatory protein of hepatitis B virus (HBV), augments viral DNA replication by stimulating viral transcription. Among numerous reported HBx-binding proteins, DDB1 has drawn attention, because DDB1 acts as a substrate receptor of the Cul4-DDB1 ubiquitin E3 ligase. Previous work reported that the DDB1-HBx interaction is indispensable for HBx-stimulated viral DNA replication, suggesting that the Cul4-DDB1 ubiquitin E3 ligase might target cellular restriction factors for ubiquitination and proteasomal degradation...
November 1, 2016: Journal of Virology
Sumedha Bagga, Siddhartha Rawat, Marcia Ajenjo, Michael J Bouchard
Chronic HBV infection is a risk factor for hepatocellular carcinoma (HCC). The HBV HBx protein stimulates HBV replication and likely influences the development of HBV-associated HCC. Whether HBx affects regulators of metabolism in normal hepatocytes has not been addressed. We used an ex vivo, cultured primary rat hepatocyte system to assess the interplay between HBV replication and mechanistic target of rapamycin complex 1 (mTORC1) signaling. HBx activated mTORC1 signaling; however, inhibition of mTORC1 enhanced HBV replication...
November 2016: Virology
Manikankana Bandopadhyay, Neelakshi Sarkar, Sibnarayan Datta, Dipanwita Das, Ananya Pal, Rajesh Panigrahi, Arup Banerjee, Chinmay K Panda, Chandrima Das, Shekhar Chakrabarti, Runu Chakravarty
BACKGROUND: Hepatitis B virus (HBV) X protein (HBx) reported to be associated with pathogenesis of hepatocellular carcinoma (HCC) and miR-122 expression is down regulated in HCC. Previous studies reported miR-122 targets cyclin G1 (CCNG1) expression and this in turn abolishes p53-mediated inhibition of HBV replication. Here we investigated the involvement of HBx protein in the modulation of miR-122 expression in hepatoblastoma cells. METHODS: Expression of miR-122 was measured in HepG2 cells transfected with HBx plasmid (HBx-HepG2), full length HBV genome (HBV-HepG2) and in constitutively HBV synthesizing HepG2...
2016: Infectious Agents and Cancer
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