Login Register Cart 0
Generic placeholder image

Infectious Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5265
ISSN (Online): 2212-3989

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

An Integrative Gene Expression Microarray Meta-analysis Identifies Host Factors and Key Signatures Involved in Hepatitis B Virus Infection

Author(s): Mohcine Elmessaoudi-Idrissi, Marc P. Windisch, Anass Kettani, Haya Altawalah, Pascal Pineau, Soumaya Benjelloun and Sayeh Ezzikouri*

Volume 20, Issue 5, 2020

Page: [698 - 707] Pages: 10

DOI: 10.2174/1871526519666190807153901

Price: $65

Abstract

Hepatitis B virus (HBV) is a global health concern. Viral and host factors orchestrate the natural history of HBV infection, but the impact of host factors that influence the clinical course of the disease remains poorly understood. The aim of this study was to identify host factors crucial to the HBV life cycle by conducting a meta-analysis utilizing public microarray datasets.

Methods: An integrative meta-analysis of expression data from two microarray datasets of HBVinfected liver tissues and healthy uninfected livers was conducted to identify gene expression signatures and overlapping biological processes modulating infection/disease.

Results: Using integrative meta-analysis of expression data (INMEX), we identified across two datasets a total of 841 genes differentially expressed during HBV infection, including 473 upregulated and 368 downregulated genes. In addition, through functional enrichment and pathway analysis, we observed that Jak-STAT, TLR, and NF-κB are the most relevant signaling pathways in chronic HBV infection. The network-based meta-analysis identified NEDD8, SKP2, JUN, and HIF1A as the most highly ranked hub genes.

Conclusion: Thus, these results may provide valuable information about novel potential host factors modulating chronic HBV infection. Such factors may serve as potential targets for the development of novel therapeutics such as activin receptor-like kinase inhibitors.

Keywords: HBV, meta-analysis, gene, expression, gene network, host factors.

[1]
Schweitzer, A.; Horn, J.; Mikolajczyk, R.T.; Krause, G.; Ott, J.J. Estimations of worldwide prevalence of chronic hepatitis B virus infection: A systematic review of data published between 1965 and 2013. Lancet, 2015, 386(10003), 1546-1555.
[http://dx.doi.org/10.1016/S0140-6736(15)61412-X] [PMID: 26231459]
[2]
Subic, M.; Zoulim, F. How to improve access to therapy in hepatitis B patients. Liver Int., 2018, 38(Suppl. 1), 115-121.
[http://dx.doi.org/10.1111/liv.13640] [PMID: 29427482]
[3]
Stein, L.L.; Loomba, R. Drug targets in hepatitis B virus infection. Infect. Disord. Drug Targets, 2009, 9(2), 105-116.
[http://dx.doi.org/10.2174/187152609787847677] [PMID: 19275699]
[4]
Zoulim, F.; Locarnini, S. Management of treatment failure in chronic hepatitis B. J. Hepatol., 2012, 56(Suppl. 1), S112-S122.
[http://dx.doi.org/10.1016/S0168-8278(12)60012-9] [PMID: 22300461]
[5]
He, Y-L.; Zhao, Y-R.; Zhang, S-L.; Lin, S-M. Host susceptibility to persistent hepatitis B virus infection. World J. Gastroenterol., 2006, 12(30), 4788-4793.
[http://dx.doi.org/10.3748/wjg.v12.i30.4788] [PMID: 16937459]
[6]
Li, T.; Liu, F.; Zhang, L.; Ye, Q.; Fan, X.; Xue, Y.; Wang, L. Host genetic factors in predicting response status in chronic hepatitis B patients discontinuing nucleos(t)ide analogs. Saudi J. Gastroenterol., 2018, 24(1), 30-36.
[http://dx.doi.org/10.4103/sjg.SJG_228_17] [PMID: 29451182]
[7]
Chen, C-J.; Yang, H-I.; Iloeje, U.H. Hepatitis B virus DNA levels and outcomes in chronic hepatitis B. Hepatology, 2009, 49(5)(Suppl.), S72-S84.
[http://dx.doi.org/10.1002/hep.22884] [PMID: 19399801]
[8]
Dandri, M.; Locarnini, S. New insight in the pathobiology of hepatitis B virus infection. Gut, 2012, 61(Suppl. 1), i6-i17.
[http://dx.doi.org/10.1136/gutjnl-2012-302056] [PMID: 22504921]
[9]
Slonim, D.K.; Yanai, I. Getting started in gene expression microarray analysis. PLOS Comput. Biol., 2009, 5(10)e1000543
[http://dx.doi.org/10.1371/journal.pcbi.1000543] [PMID: 19876380]
[10]
Haidich, A.B. Meta-analysis in medical research. Hippokratia, 2010, 14(Suppl. 1), 29-37.
[PMID: 21487488]
[11]
Oakes, M. The logic and role of meta-analysis in clinical research. Stat. Methods Med. Res., 1993, 2(2), 147-160.
[http://dx.doi.org/10.1177/096228029300200203] [PMID: 8261255]
[12]
Campain, A.; Yang, Y.H. Comparison study of microarray meta-analysis methods. BMC Bioinformatics, 2010, 11, 408.
[http://dx.doi.org/10.1186/1471-2105-11-408] [PMID: 20678237]
[13]
Xia, J.; Fjell, C.D.; Mayer, M.L.; Pena, O.M.; Wishart, D.S.; Hancock, R.E.W. INMEX--a web-based tool for integrative metaanalysis of expression data. Nucleic Acids Res., 2013, 41(Web Server issue), W63-70.
[http://dx.doi.org/10.1093/nar/gkt338] [PMID: 23766290]
[14]
Edgar, R.; Domrachev, M.; Lash, A.E. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res., 2002, 30(1), 207-210.
[http://dx.doi.org/10.1093/nar/30.1.207] [PMID: 11752295]
[15]
Kolesnikov, N.; Hastings, E.; Keays, M.; Melnichuk, O.; Tang, Y.A.; Williams, E.; Dylag, M.; Kurbatova, N.; Brandizi, M.; Burdett, T.; Megy, K.; Pilicheva, E.; Rustici, G.; Tikhonov, A.; Parkinson, H.; Petryszak, R.; Sarkans, U.; Brazma, A. ArrayExpress update--simplifying data submissions. Nucleic Acids Res., 2015, 43(Database issue), D1113-D1116.
[http://dx.doi.org/10.1093/nar/gku1057] [PMID: 25361974]
[16]
Liberati, A.; Altman, D.G.; Tetzlaff, J.; Mulrow, C.; Gøtzsche, P.C.; Ioannidis, J.P.A.; Clarke, M.; Devereaux, P.J.; Kleijnen, J.; Moher, D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration. PLoS Med., 2009, 6(7)e1000100
[http://dx.doi.org/10.1371/journal.pmed.1000100] [PMID: 19621070]
[17]
Gautier, L.; Cope, L.; Bolstad, B.M.; Irizarry, R.A. affy--analysis of Affymetrix GeneChip data at the probe level. Bioinformatics, 2004, 20(3), 307-315.
[http://dx.doi.org/10.1093/bioinformatics/btg405] [PMID: 14960456]
[18]
Johnson, W.E.; Li, C.; Rabinovic, A. Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics, 2007, 8(1), 118-127.
[http://dx.doi.org/10.1093/biostatistics/kxj037] [PMID: 16632515]
[19]
Choi, J.K.; Yu, U.; Kim, S.; Yoo, O.J. Combining multiple microarray studies and modeling interstudy variation. Bioinformatics, 2003, 19(Suppl. 1), i84-i90.
[http://dx.doi.org/10.1093/bioinformatics/btg1010] [PMID: 12855442]
[20]
Marot, G.; Foulley, J-L.; Mayer, C-D.; Jaffrézic, F. Moderated effect size and P-value combinations for microarray meta-analyses. Bioinformatics, 2009, 25(20), 2692-2699.
[http://dx.doi.org/10.1093/bioinformatics/btp444] [PMID: 19628502]
[21]
Cochran, W.G. The Combination of Estimates from Different Experiments. Biometrics, 1954, 10, 101-129.
[http://dx.doi.org/10.2307/3001666]
[22]
Xia, J.; Gill, E.E.; Hancock, R.E.W. NetworkAnalyst for statistical, visual and network-based meta-analysis of gene expression data. Nat. Protoc., 2015, 10(6), 823-844.
[http://dx.doi.org/10.1038/nprot.2015.052] [PMID: 25950236]
[23]
Xia, J.; Benner, M.J.; Hancock, R.E.W. NetworkAnalyst--Integrative Approaches for Protein-Protein Interaction Network Analysis and Visual Exploration. Nucleic Acids Res., 2014, 42W167-174.
[http://dx.doi.org/10.1093/nar/gku443]
[24]
Shannon, P.; Markiel, A.; Ozier, O.; Baliga, N.S.; Wang, J.T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res., 2003, 13(11), 2498-2504.
[http://dx.doi.org/10.1101/gr.1239303] [PMID: 14597658]
[25]
Kanehisa, M.; Furumichi, M.; Tanabe, M.; Sato, Y.; Morishima, K. KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res., 2017, 45(D1), D353-D361.
[http://dx.doi.org/10.1093/nar/gkw1092] [PMID: 27899662]
[26]
Croft, D.; Mundo, A.F.; Haw, R.; Milacic, M.; Weiser, J.; Wu, G.; Caudy, M.; Garapati, P.; Gillespie, M.; Kamdar, M.R.; Jassal, B.; Jupe, S.; Matthews, L.; May, B.; Palatnik, S.; Rothfels, K.; Shamovsky, V.; Song, H.; Williams, M.; Birney, E.; Hermjakob, H.; Stein, L.; D’Eustachio, P. The Reactome pathway knowledgebase. Nucleic Acids Res., 2014, 42(Database issue), D472-D477.
[http://dx.doi.org/10.1093/nar/gkt1102] [PMID: 24243840]
[27]
Fabregat, A.; Jupe, S.; Matthews, L.; Sidiropoulos, K.; Gillespie, M.; Garapati, P.; Haw, R.; Jassal, B.; Korninger, F.; May, B.; Milacic, M.; Roca, C.D.; Rothfels, K.; Sevilla, C.; Shamovsky, V.; Shorser, S.; Varusai, T.; Viteri, G.; Weiser, J.; Wu, G.; Stein, L.; Hermjakob, H.; D’Eustachio, P. The Reactome Pathway Knowledgebase. Nucleic Acids Res., 2018, 46(D1), D649-D655.
[http://dx.doi.org/10.1093/nar/gkx1132] [PMID: 29145629]
[28]
Kanehisa, M.; Sato, Y.; Kawashima, M.; Furumichi, M.; Tanabe, M. KEGG as a reference resource for gene and protein annotation. Nucleic Acids Res., 2016, 44(D1), D457-D462.
[http://dx.doi.org/10.1093/nar/gkv1070] [PMID: 26476454]
[29]
Kanehisa, M.; Goto, S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res., 2000, 28(1), 27-30.
[http://dx.doi.org/10.1093/nar/28.1.27] [PMID: 10592173]
[30]
Zhou, W.; Ma, Y.; Zhang, J.; Hu, J.; Zhang, M.; Wang, Y.; Li, Y.; Wu, L.; Pan, Y.; Zhang, Y.; Zhang, X.; Zhang, X.; Zhang, Z.; Zhang, J.; Li, H.; Lu, L.; Jin, L.; Wang, J.; Yuan, Z.; Liu, J. Predictive model for inflammation grades of chronic hepatitis B: Large-scale analysis of clinical parameters and gene expressions. Liver Int., 2017, 37(11), 1632-1641.
[http://dx.doi.org/10.1111/liv.13427] [PMID: 28328162]
[31]
Marshall, A.; Lukk, M.; Kutter, C.; Davies, S.; Alexander, G.; Odom, D.T. Global gene expression profiling reveals SPINK1 as a potential hepatocellular carcinoma marker. PLoS One, 2013, 8(3)e59459
[http://dx.doi.org/10.1371/journal.pone.0059459] [PMID: 23527199]
[32]
Miller, M.; Tam, A.B.; Cho, J.Y.; Doherty, T.A.; Pham, A.; Khorram, N.; Rosenthal, P.; Mueller, J.L.; Hoffman, H.M.; Suzukawa, M.; Niwa, M.; Broide, D.H. ORMDL3 is an inducible lung epithelial gene regulating metalloproteases, chemokines, OAS, and ATF6. Proc. Natl. Acad. Sci. USA, 2012, 109(41), 16648-16653.
[http://dx.doi.org/10.1073/pnas.1204151109] [PMID: 23011799]
[33]
Das, S.; Miller, M.; Broide, D.H. Chromosome 17q21 Genes ORMDL3 and GSDMB in Asthma and Immune Diseases. Adv. Immunol., 2017, 135, 1-52.
[http://dx.doi.org/10.1016/bs.ai.2017.06.001] [PMID: 28826527]
[34]
Ma, X.; Long, F.; Yun, Y.; Dang, J.; Wei, S.; Zhang, Q.; Li, J.; Zhang, H.; Zhang, W.; Wang, Z.; Liu, Q.; Zou, C. ORMDL3 and its implication in inflammatory disorders. Int. J. Rheum. Dis., 2018, 21(6), 1154-1162.
[http://dx.doi.org/10.1111/1756-185X.13324] [PMID: 29879314]
[35]
Moffatt, M.F.; Gut, I.G.; Demenais, F.; Strachan, D.P.; Bouzigon, E.; Heath, S.; von Mutius, E.; Farrall, M.; Lathrop, M.; Cookson, W.O.C.M. A large-scale, consortium-based genomewide association study of asthma. N. Engl. J. Med., 2010, 363(13), 1211-1221.
[http://dx.doi.org/10.1056/NEJMoa0906312] [PMID: 20860503]
[36]
Moffatt, M.F.; Kabesch, M.; Liang, L.; Dixon, A.L.; Strachan, D.; Heath, S.; Depner, M.; von Berg, A.; Bufe, A.; Rietschel, E.; Heinzmann, A.; Simma, B.; Frischer, T.; Willis-Owen, S.A.G.; Wong, K.C.C.; Illig, T.; Vogelberg, C.; Weiland, S.K.; von Mutius, E.; Abecasis, G.R.; Farrall, M.; Gut, I.G.; Lathrop, G.M.; Cookson, W.O.C. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature, 2007, 448(7152), 470-473.
[http://dx.doi.org/10.1038/nature06014] [PMID: 17611496]
[37]
Calışkan, M.; Bochkov, Y.A.; Kreiner-Møller, E.; Bønnelykke, K.; Stein, M.M.; Du, G.; Bisgaard, H.; Jackson, D.J.; Gern, J.E.; Lemanske, R.F., Jr; Nicolae, D.L.; Ober, C. Rhinovirus wheezing illness and genetic risk of childhood-onset asthma. N. Engl. J. Med., 2013, 368(15), 1398-1407.
[http://dx.doi.org/10.1056/NEJMoa1211592] [PMID: 23534543]
[38]
Hevezi, P.A.; Tom, E.; Wilson, K.; Lambert, P.; Gutierrez-Reyes, G.; Kershenobich, D.; Zlotnik, A. Gene expression patterns in livers of Hispanic patients infected with hepatitis C virus. Autoimmunity, 2011, 44(7), 532-542.
[http://dx.doi.org/10.3109/08916934.2011.592881] [PMID: 21864061]
[39]
You, L.H.; Zhu, L.J.; Yang, L.; Shi, C.M.; Pang, L.X.; Zhang, J.; Cui, X.W.; Ji, C.B.; Guo, X.R. Transcriptome analysis reveals the potential contribution of long noncoding RNAs to brown adipocyte differentiation. Mol. Genet. Genomics, 2015, 290(5), 1659-1671.
[http://dx.doi.org/10.1007/s00438-015-1026-6] [PMID: 25773316]
[40]
Cui, J.; Sun, W.; Hao, X.; Wei, M.; Su, X.; Zhang, Y.; Su, L.; Liu, X. EHMT2 inhibitor BIX-01294 induces apoptosis through PMAIP1-USP9X-MCL1 axis in human bladder cancer cells. Cancer Cell Int., 2015, 15(1), 4.
[http://dx.doi.org/10.1186/s12935-014-0149-x] [PMID: 25685062]
[41]
Wang, Q.; Li, N.; Wang, X.; Shen, J.; Hong, X.; Yu, H.; Zhang, Y.; Wan, T.; Zhang, L.; Wang, J.; Cao, X. Membrane protein hMYADM preferentially expressed in myeloid cells is up-regulated during differentiation of stem cells and myeloid leukemia cells. Life Sci., 2007, 80(5), 420-429.
[http://dx.doi.org/10.1016/j.lfs.2006.09.043] [PMID: 17097684]
[42]
Isidor, B.; Küry, S.; Rosenfeld, J.A.; Besnard, T.; Schmitt, S.; Joss, S.; Davies, S.J.; Lebel, R.R.; Henderson, A.; Schaaf, C.P.; Streff, H.E.; Yang, Y.; Jain, V.; Chida, N.; Latypova, X.; Le Caignec, C.; Cogné, B.; Mercier, S.; Vincent, M.; Colin, E.; Bonneau, D.; Denommé, A-S.; Parent, P.; Gilbert-Dussardier, B.; Odent, S.; Toutain, A.; Piton, A.; Dina, C.; Donnart, A.; Lindenbaum, P.; Charpentier, E.; Redon, R.; Iemura, K.; Ikeda, M.; Tanaka, K.; Bézieau, S. De Novo Truncating Mutations in the Kinetochore-Microtubules Attachment Gene CHAMP1 Cause Syndromic Intellectual Disability. Hum. Mutat., 2016, 37(4), 354-358.
[http://dx.doi.org/10.1002/humu.22952] [PMID: 26751395]
[43]
Tan, C-C.; Li, G-X.; Tan, L-D.; Du, X.; Li, X-Q.; He, R.; Wang, Q-S.; Feng, Y-M. Breast cancer cells obtain an osteomimetic feature via epithelial-mesenchymal transition that have undergone BMP2/RUNX2 signaling pathway induction. Oncotarget, 2016, 7(48), 79688-79705.
[http://dx.doi.org/10.18632/oncotarget.12939] [PMID: 27806311]
[44]
Liu, T.; Sun, H.; Liu, S.; Yang, Z.; Li, L.; Yao, N.; Cheng, S.; Dong, X.; Liang, X.; Chen, C.; Wang, Y.; Zhao, X. The suppression of DUSP5 expression correlates with paclitaxel resistance and poor prognosis in basal-like breast cancer. Int. J. Med. Sci., 2018, 15(7), 738-747.
[http://dx.doi.org/10.7150/ijms.24981] [PMID: 29910679]
[45]
Makise, N.; Sekimizu, M.; Kobayashi, E.; Yoshida, H.; Fukayama, M.; Kato, T.; Kawai, A.; Ichikawa, H.; Yoshida, A. A. Low-Grade Endometrial Stromal Sarcoma with a Novel MEAF6-SUZ12 Fusion. Virchows Arch. Int. J. Pathol., 2019.
[46]
Meng, L.; Wang, M.; Du, Z.; Fang, Z.; Wu, B.; Wu, J.; Xie, W.; Shen, J.; Zhu, T.; Xu, X.; Liao, L.; Xu, L.; Li, E.; Lan, B. Cell Signaling Pathway in 12-O-Tetradecanoylphorbol-13-acetate-Induced LCN2 Gene Transcription in Esophageal Squamous Cell Carcinoma. BioMed Res. Int., 2017.20179592501
[http://dx.doi.org/10.1155/2017/9592501] [PMID: 29098164]
[47]
Thomas, E.; Baumert, T.F.; Hepatitis, B.; Hepatitis, B. Virus-Hepatocyte Interactions and Innate Immune Responses: Experimental Models and Molecular Mechanisms. Semin. Liver Dis., 2019.
[http://dx.doi.org/10.1055/s-0039-1685518] [PMID: 31266064]
[48]
Zang, M.; Li, Y.; He, H.; Ding, H.; Chen, K.; Du, J.; Chen, T.; Wu, Z.; Liu, H.; Wang, D.; Cai, J.; Qu, C. IL-23 production of liver inflammatory macrophages to damaged hepatocytes promotes hepatocellular carcinoma development after chronic hepatitis B virus infection. Biochim. Biophys. Acta Mol. Basis Dis., 2018, 1864(12), 3759-3770.
[http://dx.doi.org/10.1016/j.bbadis.2018.10.004] [PMID: 30292634]
[49]
Hopcraft, S.E.; Damania, B. Tumour viruses and innate immunity. Philos. Trans. R. Soc. Lond. B Biol. Sci., 2017, 372(1732), 372.
[http://dx.doi.org/10.1098/rstb.2016.0267] [PMID: 28893934]
[50]
Chen, Z.; Yu, W.; Zhou, Q.; Zhang, J.; Jiang, H.; Hao, D.; Wang, J.; Zhou, Z.; He, C.; Xiao, Z. A Novel lncRNA IHS Promotes Tumor Proliferation and Metastasis in HCC by Regulating the ERK- and AKT/GSK-3β-Signaling Pathways. Mol. Ther. Nucleic Acids, 2019, 16, 707-720.
[http://dx.doi.org/10.1016/j.omtn.2019.04.021] [PMID: 31128422]
[51]
Du, X.X.; Shi, Y.; Yang, Y.; Yu, Y.; Lou, H.G.; Lv, F.F.; Chen, Z.; Yang, Q. DAMP molecular IL-33 augments monocytic inflammatory storm in hepatitis B-precipitated acute-on-chronic liver failure. Liver Int., 2018, 38(2), 229-238.
[http://dx.doi.org/10.1111/liv.13503] [PMID: 28640516]
[52]
Cheng, X.; Xia, Y.; Serti, E.; Block, P.D.; Chung, M.; Chayama, K.; Rehermann, B.; Liang, T.J.; Hepatitis, B. Hepatitis B virus evades innate immunity of hepatocytes but activates cytokine production by macrophages. Hepatology, 2017, 66(6), 1779-1793.
[http://dx.doi.org/10.1002/hep.29348] [PMID: 28665004]
[53]
Honda, M.; Yamashita, T.; Ueda, T.; Takatori, H.; Nishino, R.; Kaneko, S. Different signaling pathways in the livers of patients with chronic hepatitis B or chronic hepatitis C. Hepatology, 2006, 44(5), 1122-1138.
[http://dx.doi.org/10.1002/hep.21383] [PMID: 17058214]
[54]
Tessoulin, B.; Papin, A.; Gomez-Bougie, P.; Bellanger, C.; Amiot, M.; Pellat-Deceunynck, C.; Chiron, D. BCL2-Family Dysregulation in B-Cell Malignancies: From Gene Expression Regulation to a Targeted Therapy Biomarker. Front. Oncol., 2019, 8, 645.
[http://dx.doi.org/10.3389/fonc.2018.00645] [PMID: 30666297]
[55]
Zhao, B-B.; Zheng, S-J.; Gong, L-L.; Wang, Y.; Chen, C-F.; Jin, W-J.; Zhang, D.; Yuan, X-H.; Guo, J.; Duan, Z-P.; He, Y-W. T lymphocytes from chronic HCV-infected patients are primed for activation-induced apoptosis and express unique pro-apoptotic gene signature. PLoS One, 2013, 8(10)e77008
[http://dx.doi.org/10.1371/journal.pone.0077008] [PMID: 24130824]
[56]
Albers, M.; Kranz, H.; Kober, I.; Kaiser, C.; Klink, M.; Suckow, J.; Kern, R.; Koegl, M. Automated yeast two-hybrid screening for nuclear receptor-interacting proteins. Mol. Cell. Proteomics, 2005, 4(2), 205-213.
[http://dx.doi.org/10.1074/mcp.M400169-MCP200] [PMID: 15604093]
[57]
Zhou, D.; Quach, K.M.; Yang, C.; Lee, S.Y.; Pohajdak, B.; Chen, S. PNRC: A proline-rich nuclear receptor coregulatory protein that modulates transcriptional activation of multiple nuclear receptors including orphan receptors SF1 (steroidogenic factor 1) and ERRalpha1 (estrogen related receptor alpha-1). Mol. Endocrinol., 2000, 14(7), 986-998.
[PMID: 10894149]
[58]
Petroski, M.D.; Deshaies, R.J. Function and regulation of cullin-RING ubiquitin ligases. Nat. Rev. Mol. Cell Biol., 2005, 6(1), 9-20.
[http://dx.doi.org/10.1038/nrm1547] [PMID: 15688063]
[59]
Rabut, G.; Peter, M. Function and regulation of protein neddylation. ‘Protein modifications: Beyond the usual suspects’ review series. EMBO Rep., 2008, 9(10), 969-976.
[http://dx.doi.org/10.1038/embor.2008.183] [PMID: 18802447]
[60]
Liu, N.; Zhang, J.; Yang, X.; Jiao, T.; Zhao, X.; Li, W.; Zhu, J.; Yang, P.; Jin, J.; Peng, J.; Li, Z.; Ye, X. HDM2 Promotes NEDDylation of Hepatitis B Virus HBx To Enhance Its Stability and Function. J. Virol., 2017, 91(16), 91.
[http://dx.doi.org/10.1128/JVI.00340-17] [PMID: 28592528]
[61]
Decorsière, A.; Mueller, H.; van Breugel, P.C.; Abdul, F.; Gerossier, L.; Beran, R.K.; Livingston, C.M.; Niu, C.; Fletcher, S.P.; Hantz, O.; Strubin, M.; Hepatitis, B.; Virus, X. Hepatitis B virus X protein identifies the Smc5/6 complex as a host restriction factor. Nature, 2016, 531(7594), 386-389.
[http://dx.doi.org/10.1038/nature17170] [PMID: 26983541]
[62]
Sekiba, K.; Otsuka, M.; Ohno, M.; Yamagami, M.; Kishikawa, T.; Seimiya, T.; Suzuki, T.; Tanaka, E.; Ishibashi, R.; Funato, K.; Koike, K. Pevonedistat, a First-in-Class NEDD8-Activating Enzyme Inhibitor, Is a Potent Inhibitor of Hepatitis B Virus; Hepatol; Baltim: Md, 2018.
[63]
Chen, G.; Wang, Y.; Garate, M.; Zhou, J.; Li, G. The tumor suppressor ING3 is degraded by SCF(Skp2)-mediated ubiquitin-proteasome system. Oncogene, 2010, 29(10), 1498-1508.
[http://dx.doi.org/10.1038/onc.2009.424] [PMID: 19935701]
[64]
Kalra, N.; Kumar, V. The X protein of hepatitis B virus binds to the F box protein Skp2 and inhibits the ubiquitination and proteasomal degradation of c-Myc. FEBS Lett., 2006, 580(2), 431-436.
[http://dx.doi.org/10.1016/j.febslet.2005.12.034] [PMID: 16376880]
[65]
Chen, L.; Gu, L.; Gu, Y.; Wang, H.; Deng, M.; Stamataki, Z.; Oo, Y.H.; Huang, Y. HBV core promoter mutations and AKT upregulate S-phase kinase-associated protein 2 to promote postoperative hepatocellular carcinoma progression. Sci. Rep., 2016, 6, 35917.
[http://dx.doi.org/10.1038/srep35917] [PMID: 27779207]
[66]
Lee, S.; Kim, W.; Ko, C.; Ryu, W-S.; Hepatitis, B.; Virus, X. Hepatitis B virus X protein enhances Myc stability by inhibiting SCF(Skp2) ubiquitin E3 ligase-mediated Myc ubiquitination and contributes to oncogenesis. Oncogene, 2016, 35(14), 1857-1867.
[http://dx.doi.org/10.1038/onc.2015.251] [PMID: 26165841]
[67]
Bossy-Wetzel, E.; Bakiri, L.; Yaniv, M. Induction of apoptosis by the transcription factor c-Jun. EMBO J., 1997, 16(7), 1695-1709.
[http://dx.doi.org/10.1093/emboj/16.7.1695] [PMID: 9130714]
[68]
Davis, R.J. Signal transduction by the JNK group of MAP kinases. Cell, 2000, 103(2), 239-252.
[http://dx.doi.org/10.1016/S0092-8674(00)00116-1] [PMID: 11057897]
[69]
You, H.; Kong, F.; Zhou, K.; Wei, X.; Hu, L.; Hu, W.; Luo, W.; Kou, Y.; Liu, X.; Chen, X.; Zheng, K.; Tang, R. HBX protein promotes LASP-1 expression through activation of c-Jun in human hepatoma cells. J. Cell. Physiol., 2018, 233(9), 7279-7291.
[http://dx.doi.org/10.1002/jcp.26560] [PMID: 29600594]
[70]
Guo, L.; Guo, Y.; Xiao, S.; Shi, X. Protein kinase p-JNK is correlated with the activation of AP-1 and its associated Jun family proteins in hepatocellular carcinoma. Life Sci., 2005, 77(15), 1869-1878.
[http://dx.doi.org/10.1016/j.lfs.2005.03.019] [PMID: 15927205]
[71]
Trierweiler, C.; Hockenjos, B.; Zatloukal, K.; Thimme, R.; Blum, H.E.; Wagner, E.F.; Hasselblatt, P. The transcription factor c-JUN/AP-1 promotes HBV-related liver tumorigenesis in mice. Cell Death Differ., 2016, 23(4), 576-582.
[http://dx.doi.org/10.1038/cdd.2015.121] [PMID: 26470729]
[72]
Sasaki, R.; Kanda, T.; Nakamura, M.; Nakamoto, S.; Haga, Y.; Wu, S.; Shirasawa, H.; Yokosuka, O. Possible Involvement of Hepatitis B Virus Infection of Hepatocytes in the Attenuation of Apoptosis in Hepatic Stellate Cells. PLoS One, 2016, 11(1)e0146314
[http://dx.doi.org/10.1371/journal.pone.0146314] [PMID: 26731332]
[73]
Semenza, G.L. Transcriptional regulation by hypoxia-inducible factor 1 molecular mechanisms of oxygen homeostasis. Trends Cardiovasc. Med., 1996, 6(5), 151-157.
[http://dx.doi.org/10.1016/1050-1738(96)00039-4] [PMID: 21232289]
[74]
Yoo, Y-G.; Oh, S.H.; Park, E.S.; Cho, H.; Lee, N.; Park, H.; Kim, D.K.; Yu, D-Y.; Seong, J.K.; Lee, M-O.; Hepatitis, B.; Virus, X. Hepatitis B virus X protein enhances transcriptional activity of hypoxia-inducible factor-1alpha through activation of mitogen-activated protein kinase pathway. J. Biol. Chem., 2003, 278(40), 39076-39084.
[http://dx.doi.org/10.1074/jbc.M305101200] [PMID: 12855680]
[75]
Chen, J.; Xu, W.; Chen, Y.; Xie, X.; Zhang, Y.; Ma, C.; Yang, Q.; Han, Y.; Zhu, C.; Xiong, Y.; Wu, K.; Liu, F.; Liu, Y.; Wu, J. Matrix Metalloproteinase 9 Facilitates Hepatitis B Virus Replication through Binding with Type I Interferon (IFN) Receptor 1 To Repress IFN/JAK/STAT Signaling. J. Virol., 2017, 91(8), 91.
[http://dx.doi.org/10.1128/JVI.01824-16] [PMID: 28122987]
[76]
Lin, Y.; Huang, X.; Wu, J.; Liu, J.; Chen, M.; Ma, Z.; Zhang, E.; Liu, Y.; Huang, S.; Li, Q.; Zhang, X.; Hou, J.; Yang, D.; Lu, M.; Xu, Y. Pre-Activation of Toll-Like Receptor 2 Enhances CD8+ T-Cell Responses and Accelerates Hepatitis B Virus Clearance in the Mouse Models. Front. Immunol., 2018, 9, 1495.
[http://dx.doi.org/10.3389/fimmu.2018.01495] [PMID: 30008718]
[77]
Christensen, J.; Agger, K.; Cloos, P.A.C.; Pasini, D.; Rose, S.; Sennels, L.; Rappsilber, J.; Hansen, K.H.; Salcini, A.E.; Helin, K. RBP2 belongs to a family of demethylases, specific for tri-and dimethylated lysine 4 on histone 3. Cell, 2007, 128(6), 1063-1076.
[http://dx.doi.org/10.1016/j.cell.2007.02.003] [PMID: 17320161]
[78]
Wang, D.; Han, S.; Peng, R.; Jiao, C.; Wang, X.; Yang, X.; Yang, R.; Li, X. Depletion of histone demethylase KDM5B inhibits cell proliferation of hepatocellular carcinoma by regulation of cell cycle checkpoint proteins p15 and p27. J. Exp. Clin. Cancer Res., 2016, 35, 37.
[http://dx.doi.org/10.1186/s13046-016-0311-5] [PMID: 26911146]
[79]
Shigekawa, Y.; Hayami, S.; Ueno, M.; Miyamoto, A.; Suzaki, N.; Kawai, M.; Hirono, S.; Okada, K-I.; Hamamoto, R.; Yamaue, H. Overexpression of KDM5B/JARID1B is associated with poor prognosis in hepatocellular carcinoma. Oncotarget, 2018, 9(76), 34320-34335.
[http://dx.doi.org/10.18632/oncotarget.26144] [PMID: 30344945]
[80]
Hayami, S.; Yoshimatsu, M.; Veerakumarasivam, A.; Unoki, M.; Iwai, Y.; Tsunoda, T.; Field, H.I.; Kelly, J.D.; Neal, D.E.; Yamaue, H.; Ponder, B.A.J.; Nakamura, Y.; Hamamoto, R. Overexpression of the JmjC histone demethylase KDM5B in human carcinogenesis: Involvement in the proliferation of cancer cells through the E2F/RB pathway. Mol. Cancer, 2010, 9, 59.
[http://dx.doi.org/10.1186/1476-4598-9-59] [PMID: 20226085]
[81]
Ohta, K.; Haraguchi, N.; Kano, Y.; Kagawa, Y.; Konno, M.; Nishikawa, S.; Hamabe, A.; Hasegawa, S.; Ogawa, H.; Fukusumi, T.; Uemura, M.; Nishimura, J.; Hata, T.; Takemasa, I.; Mizushima, T.; Noguchi, Y.; Ozaki, M.; Kudo, T.; Sakai, D.; Satoh, T.; Fukami, M.; Ishii, M.; Yamamoto, H.; Doki, Y.; Mori, M.; Ishii, H. Depletion of JARID1B induces cellular senescence in human colorectal cancer. Int. J. Oncol., 2013, 42(4), 1212-1218.
[http://dx.doi.org/10.3892/ijo.2013.1799] [PMID: 23354547]
[82]
Dai, B.; Hu, Z.; Huang, H.; Zhu, G.; Xiao, Z.; Wan, W.; Zhang, P.; Jia, W.; Zhang, L. Overexpressed KDM5B is associated with the progression of glioma and promotes glioma cell growth via downregulating p21. Biochem. Biophys. Res. Commun., 2014, 454(1), 221-227.
[http://dx.doi.org/10.1016/j.bbrc.2014.10.078] [PMID: 25450384]
[83]
Wang, X.; Oishi, N.; Shimakami, T.; Yamashita, T.; Honda, M.; Murakami, S.; Kaneko, S.; Hepatitis, B.; Virus, X. Hepatitis B virus X protein induces hepatic stem cell-like features in hepatocellular carcinoma by activating KDM5B. World J. Gastroenterol., 2017, 23(18), 3252-3261.
[http://dx.doi.org/10.3748/wjg.v23.i18.3252] [PMID: 28566884]
[84]
Piechaczyk, M.; Farràs, R. Regulation and function of JunB in cell proliferation. Biochem. Soc. Trans., 2008, 36(Pt 5), 864-867.
[http://dx.doi.org/10.1042/BST0360864] [PMID: 18793152]
[85]
Tedesco, D.; Haragsim, L. Cyclosporine: A review. J. Transplant., 2012.2012230386
[http://dx.doi.org/10.1155/2012/230386] [PMID: 22263104]
[86]
Borel, J.F.; Gunn, H.C. Cyclosporine as a new approach to therapy of autoimmune diseases. Ann. N. Y. Acad. Sci., 1986, 475, 307-319.
[http://dx.doi.org/10.1111/j.1749-6632.1986.tb20879.x] [PMID: 3538973]
[87]
Iwamoto, M.; Watashi, K.; Tsukuda, S.; Aly, H.H.; Fukasawa, M.; Fujimoto, A.; Suzuki, R.; Aizaki, H.; Ito, T.; Koiwai, O.; Kusuhara, H.; Wakita, T. Evaluation and identification of hepatitis B virus entry inhibitors using HepG2 cells overexpressing a membrane transporter NTCP. Biochem. Biophys. Res. Commun., 2014, 443(3), 808-813.
[http://dx.doi.org/10.1016/j.bbrc.2013.12.052] [PMID: 24342612]
[88]
Liu, X-J.; Ruan, C-M.; Gong, X-F.; Li, X-Z.; Wang, H-L.; Wang, M-W.; Yin, J.Q. Antagonism of transforming growth factor-Beta signaling inhibits fibrosis-related genes. Biotechnol. Lett., 2005, 27(20), 1609-1615.
[http://dx.doi.org/10.1007/s10529-005-2516-0] [PMID: 16245182]
[89]
Murata, M.; Matsuzaki, K.; Yoshida, K.; Sekimoto, G.; Tahashi, Y.; Mori, S.; Uemura, Y.; Sakaida, N.; Fujisawa, J.; Seki, T.; Kobayashi, K.; Yokote, K.; Koike, K.; Okazaki, K.; Hepatitis, B.; Virus, X. Hepatitis B virus X protein shifts human hepatic transforming growth factor (TGF)-beta signaling from tumor suppression to oncogenesis in early chronic hepatitis B. Hepatology, 2009, 49(4), 1203-1217.
[http://dx.doi.org/10.1002/hep.22765] [PMID: 19263472]

Rights & Permissions Print Cite
Article Metrics
15
2
© 2024 Bentham Science Publishers | Privacy Policy