{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T12:35:28Z","timestamp":1767962128605,"version":"3.49.0"},"reference-count":75,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Syst Biol"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide, and the mechanisms that lead to the disease are still relatively unclear. However, with the development of high-throughput technologies it is possible to gain a systematic view of biological systems to enhance the understanding of the roles of genes associated with HCC. Thus, analysis of the mechanism of molecule interactions in the context of gene regulatory networks can reveal specific sub-networks that lead to the development of HCC.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In this study, we aimed to identify the most important gene regulations that are dysfunctional in HCC generation. Our method for constructing gene regulatory network is based on predicted target interactions, experimentally-supported interactions, and co-expression model. Regulators in the network included both transcription factors and microRNAs to provide a complete view of gene regulation. Analysis of gene regulatory network revealed that gene regulation in HCC is highly modular, in which different sets of regulators take charge of specific biological processes. We found that microRNAs mainly control biological functions related to mitochondria and oxidative reduction, while transcription factors control immune responses, extracellular activity and the cell cycle. On the higher level of gene regulation, there exists a core network that organizes regulations between different modules and maintains the robustness of the whole network. There is direct experimental evidence for most of the regulators in the core gene regulatory network relating to HCC. We infer it is the central controller of gene regulation. Finally, we explored the influence of the core gene regulatory network on biological pathways.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our analysis provides insights into the mechanism of transcriptional and post-transcriptional control in HCC. In particular, we highlight the importance of the core gene regulatory network; we propose that it is highly related to HCC and we believe further experimental validation is worthwhile.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-0509-6-32","type":"journal-article","created":{"date-parts":[[2012,5,1]],"date-time":"2012-05-01T16:14:25Z","timestamp":1335888865000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Gene regulation is governed by a core network in hepatocellular carcinoma"],"prefix":"10.1186","volume":"6","author":[{"given":"Zuguang","family":"Gu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2012,5,1]]},"reference":[{"key":"892_CR1","doi-asserted-by":"publisher","first-page":"69","DOI":"10.3322\/caac.20107","volume":"61","author":"A Jemal","year":"2011","unstructured":"Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin 2011, 61: 69-90. 10.3322\/caac.20107","journal-title":"CA Cancer J Clin"},{"key":"892_CR2","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1038\/nrc1934","volume":"6","author":"PA Farazi","year":"2006","unstructured":"Farazi PA, DePinho RA: Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer 2006, 6: 674-87. 10.1038\/nrc1934","journal-title":"Nat Rev Cancer"},{"key":"892_CR3","first-page":"1662","volume":"295","author":"H Kitano","year":"2002","unstructured":"Kitano H: Systems biology: a brief overview. Science. 2002, 295: 1662-4.","journal-title":"Systems biology: a brief overview. Science"},{"key":"892_CR4","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.tig.2010.05.001","volume":"26","author":"A de la Fuente","year":"2010","unstructured":"de la Fuente A: From \u201cdifferential expression\u201d to \u201cdifferential networking\u201d - identification of dysfunctional regulatory networks in diseases. Trends Genet 2010, 26: 326-33. 10.1016\/j.tig.2010.05.001","journal-title":"Trends Genet"},{"key":"892_CR5","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1016\/j.cell.2006.05.030","volume":"125","author":"L Zender","year":"2006","unstructured":"Zender L, Spector MS, Xue W, Flemming P, Cordon-Cardo C, Silke J, Fan ST, Luk JM, Wigler M, Hannon GJ, Mu D, Lucito R, Powers S, Lowe SW: Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach. Cell 2006, 125: 1253-67. 10.1016\/j.cell.2006.05.030","journal-title":"Cell"},{"key":"892_CR6","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1038\/nature03043","volume":"431","author":"CM Shachaf","year":"2004","unstructured":"Shachaf CM, Kopelman AM, Arvanitis C, Karlsson A, Beer S, Mandl S, Bachmann MH, Borowsky AD, Ruebner B, Cardiff RD, Yang Q, Bishop JM, Contag CH, Felsher DW: MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer. Nature 2004, 431: 1112-7. 10.1038\/nature03043","journal-title":"Nature"},{"key":"892_CR7","doi-asserted-by":"publisher","first-page":"5054","DOI":"10.1038\/sj.onc.1203885","volume":"19","author":"EA Conner","year":"2000","unstructured":"Conner EA, Lemmer ER, Omori M, Wirth PJ, Factor VM, Thorgeirsson SS: Dual functions of E2F-1 in a transgenic mouse model of liver carcinogenesis. Oncogene 2000, 19: 5054-62. 10.1038\/sj.onc.1203885","journal-title":"Oncogene"},{"key":"892_CR8","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/nrg2290","volume":"9","author":"W Filipowicz","year":"2008","unstructured":"Filipowicz W, Bhattacharyya SN, Sonenberg N: Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 2008, 9: 102-14.","journal-title":"Nat Rev Genet"},{"key":"892_CR9","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1007\/s13238-010-0114-y","volume":"1","author":"S Huang","year":"2010","unstructured":"Huang S, He X: microRNAs: tiny RNA molecules, huge driving forces to move the cell. Protein Cell 2010, 1: 927-34. 10.1007\/s13238-010-0114-y","journal-title":"Protein Cell"},{"key":"892_CR10","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1038\/nrc1840","volume":"6","author":"A Esquela-Kerscher","year":"2006","unstructured":"Esquela-Kerscher A, Slack FJ: Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer 2006, 6: 259-69. 10.1038\/nrc1840","journal-title":"Nat Rev Cancer"},{"key":"892_CR11","doi-asserted-by":"publisher","first-page":"7390","DOI":"10.1158\/0008-5472.CAN-06-0800","volume":"66","author":"GA Calin","year":"2006","unstructured":"Calin GA, Croce CM: MicroRNA-cancer connection: the beginning of a new tale. Cancer Res 2006, 66: 7390-4. 10.1158\/0008-5472.CAN-06-0800","journal-title":"Cancer Res"},{"key":"892_CR12","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/S1665-2681(19)31864-2","volume":"7","author":"H Varnholt","year":"2008","unstructured":"Varnholt H: The role of microRNAs in primary liver cancer. Ann Hepatol 2008, 7: 104-13.","journal-title":"Ann Hepatol"},{"key":"892_CR13","doi-asserted-by":"publisher","first-page":"6092","DOI":"10.1158\/0008-5472.CAN-06-4607","volume":"67","author":"L Gramantieri","year":"2007","unstructured":"Gramantieri L, Ferracin M, Fornari F, Veronese A, Sabbioni S, Liu CG, Calin GA, Giovannini C, Ferrazzi E, Grazi GL, Croce CM, Bolondi L, Negrini M: Cyclin G1 is a target of miR-122a, a microRNA frequently down-regulated in human hepatocellular carcinoma. Cancer Res 2007, 67: 6092-9. 10.1158\/0008-5472.CAN-06-4607","journal-title":"Cancer Res"},{"key":"892_CR14","doi-asserted-by":"publisher","first-page":"6029","DOI":"10.1158\/0008-5472.CAN-05-0137","volume":"65","author":"JA Chan","year":"2005","unstructured":"Chan JA, Krichevsky AM, Kosik KS: MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 2005, 65: 6029-33. 10.1158\/0008-5472.CAN-05-0137","journal-title":"Cancer Res"},{"key":"892_CR15","doi-asserted-by":"publisher","first-page":"e131","DOI":"10.1371\/journal.pcbi.0030131","volume":"3","author":"R Shalgi","year":"2007","unstructured":"Shalgi R, Lieber D, Oren M, Pilpel Y: Global and local architecture of the mammalian microRNA-transcription factor regulatory network. PLoS Comput Biol 2007, 3: e131. 10.1371\/journal.pcbi.0030131","journal-title":"PLoS Comput Biol"},{"key":"892_CR16","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1186\/1471-2164-10-373","volume":"10","author":"X Peng","year":"2009","unstructured":"Peng X, Li Y, Walters KA, Rosenzweig ER, Lederer SL, Aicher LD, Proll S, Katze MG: Computational identification of hepatitis C virus associated microRNA-mRNA regulatory modules in human livers. BMC Genomics 2009, 10: 373. 10.1186\/1471-2164-10-373","journal-title":"BMC Genomics"},{"key":"892_CR17","doi-asserted-by":"publisher","first-page":"5969","DOI":"10.1093\/nar\/gkp638","volume":"37","author":"K Tu","year":"2009","unstructured":"Tu K, Yu H, Hua YJ, Li YY, Liu L, Xie L, Li YX: Combinatorial network of primary and secondary microRNA-driven regulatory mechanisms. Nucleic Acids Res 2009, 37: 5969-80. 10.1093\/nar\/gkp638","journal-title":"Nucleic Acids Res"},{"issue":"Suppl 2","key":"892_CR18","doi-asserted-by":"publisher","first-page":"S22","DOI":"10.1186\/1471-2164-9-S2-S22","volume":"9","author":"G Wang","year":"2008","unstructured":"Wang G, Wang Y, Feng W, Wang X, Yang JY, Zhao Y, Wang Y, Liu Y: Transcription factor and microRNA regulation in androgen-dependent and -independent prostate cancer cells. BMC Genomics 2008,9(Suppl 2):S22. 10.1186\/1471-2164-9-S2-S22","journal-title":"BMC Genomics"},{"key":"892_CR19","doi-asserted-by":"publisher","first-page":"2438","DOI":"10.1093\/bioinformatics\/btq466","volume":"26","author":"A Lachmann","year":"2010","unstructured":"Lachmann A, Xu H, Krishnan J, Berger SI, Mazloom AR: Ma'ayan A.: ChEA: transcription factor regulation inferred from integrating genome-wide ChIP-X experiments. Bioinformatics 2010, 26: 2438-44. 10.1093\/bioinformatics\/btq466","journal-title":"Bioinformatics"},{"key":"892_CR20","doi-asserted-by":"publisher","first-page":"D222","DOI":"10.1093\/nar\/gkr1161","volume":"40","author":"T Vergoulis","year":"2012","unstructured":"Vergoulis T, Vlachos IS, Alexiou P, Georgakilas G, Maragkakis M, Reczko M, Gerangelos S, Koziris N, Dalamagas T, Hatzigeorgiou AG: TarBase 6.0: capturing the exponential growth of miRNA targets with experimental support. Nucleic Acids Res 2012, 40: D222-9. 10.1093\/nar\/gkr1161","journal-title":"Nucleic Acids Res"},{"key":"892_CR21","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/1752-0509-4-90","volume":"4","author":"C Qiu","year":"2010","unstructured":"Qiu C, Wang J, Yao P, Wang E, Cui Q: microRNA evolution in a human transcription factor and microRNA regulatory network. BMC Syst Biol 2010, 4: 90. 10.1186\/1752-0509-4-90","journal-title":"BMC Syst Biol"},{"key":"892_CR22","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1038\/msb.2010.58","volume":"6","author":"J Burchard","year":"2010","unstructured":"Burchard J, Zhang C, Liu AM, Poon RT, Lee NP, Wong KF, Sham PC, Lam BY, Ferguson MD, Tokiwa G, Smith R, Leeson B, Beard R, Lamb JR, Lim L, Mao M, Dai H, Luk JM: microRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma. Mol Syst Biol 2010, 6: 402.","journal-title":"Mol Syst Biol"},{"key":"892_CR23","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/1752-0509-4-8","volume":"4","author":"J Ruan","year":"2010","unstructured":"Ruan J, Dean AK, Zhang W: A general co-expression network-based approach to gene expression analysis: comparison and applications. BMC Syst Biol 2010, 4: 8. 10.1186\/1752-0509-4-8","journal-title":"BMC Syst Biol"},{"key":"892_CR24","doi-asserted-by":"crossref","first-page":"Article17","DOI":"10.2202\/1544-6115.1128","volume":"4","author":"B Zhang","year":"2005","unstructured":"Zhang B, Horvath S: A general framework for weighted gene co-expression network analysis. Stat Appl Genet Mol Biol 2005, 4: Article17.","journal-title":"Stat Appl Genet Mol Biol"},{"key":"892_CR25","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/nrg1272","volume":"5","author":"A-L Barab\u00e1si","year":"2004","unstructured":"Barab\u00e1si A-L, Oltvai ZN: Network biology: understanding the cell\u2019s functional organization. Nat Rev Genet 2004, 5: 101-13. 10.1038\/nrg1272","journal-title":"Nat Rev Genet"},{"key":"892_CR26","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1126\/science.286.5439.509","volume":"286","author":"A Barab\u00e1si","year":"1999","unstructured":"Barab\u00e1si A: Emergence of Scaling in Random Networks. Science 1999, 286: 509-512. 10.1126\/science.286.5439.509","journal-title":"Science"},{"key":"892_CR27","doi-asserted-by":"publisher","first-page":"138701","DOI":"10.1103\/PhysRevLett.88.138701","volume":"88","author":"S Mossa","year":"2002","unstructured":"Mossa S, Barth\u00e9l\u00e9my M, Eugene Stanley H, Nunes Amaral LA: Truncation of power law behavior in \u201cscale-free\u201d network models due to information filtering. Phys Rev Lett 2002, 88: 138701.","journal-title":"Phys Rev Lett"},{"key":"892_CR28","doi-asserted-by":"publisher","first-page":"7821","DOI":"10.1073\/pnas.122653799","volume":"99","author":"M Girvan","year":"2002","unstructured":"Girvan M, Newman MEJ: Community structure in social and biological networks. Proc Natl Acad Sci USA 2002, 99: 7821-6. 10.1073\/pnas.122653799","journal-title":"Proc Natl Acad Sci USA"},{"key":"892_CR29","first-page":"284","volume-title":"Computer and Information Sciences","author":"P Pons","year":"2005","unstructured":"Pons P, Latapy M: Computing communities in large networks using random walks. In Computer and Information Sciences. Volumn 3733 edition. Edited by: Yolum P, Gungor T, Gurgen F, Ozturan C. Springer, Berlin; 2005:284-293.","edition":"Volumn 3733"},{"key":"892_CR30","doi-asserted-by":"publisher","first-page":"4198","DOI":"10.1038\/sj.onc.1207755","volume":"23","author":"Y Ito","year":"2004","unstructured":"Ito Y: Oncogenic potential of the RUNX gene family: \u201coverview\u201d. Oncogene 2004, 23: 4198-208. 10.1038\/sj.onc.1207755","journal-title":"Oncogene"},{"key":"892_CR31","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1002\/j.1460-2075.1990.tb08283.x","volume":"9","author":"T Gerster","year":"1990","unstructured":"Gerster T, Balmaceda CG, Roeder RG: The cell type-specific octamer transcription factor OTF-2 has two domains required for the activation of transcription. EMBO J 1990, 9: 1635-43.","journal-title":"EMBO J"},{"key":"892_CR32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.gene.2005.08.007","volume":"363","author":"R Janknecht","year":"2005","unstructured":"Janknecht R: EWS-ETS oncoproteins: the linchpins of Ewing tumors. Gene 2005, 363: 1-14.","journal-title":"Gene"},{"key":"892_CR33","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1006\/geno.1996.0516","volume":"37","author":"BA Mock","year":"1996","unstructured":"Mock BA, Liu L, LePaslier D, Huang S: The B-lymphocyte maturation promoting transcription factor BLIMP1\/PRDI-BF1 maps to D6S447 on human chromosome 6q21-q22.1 and the syntenic region of mouse chromosome 10. Genomics 1996, 37: 24-8.","journal-title":"Genomics"},{"key":"892_CR34","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1111\/j.1349-7006.2003.tb01485.x","volume":"94","author":"S Hirohashi","year":"2003","unstructured":"Hirohashi S, Kanai Y: Cell adhesion system and human cancer morphogenesis. Cancer Sci 2003, 94: 575-581. 10.1111\/j.1349-7006.2003.tb01485.x","journal-title":"Cancer Sci"},{"key":"892_CR35","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1016\/j.devcel.2010.05.009","volume":"18","author":"C Yin","year":"2010","unstructured":"Yin C, Kikuchi K, Hochgreb T, Poss KD, Stainier DYR: Hand2 regulates extracellular matrix remodeling essential for gut-looping morphogenesis in zebrafish. Dev Cell 2010, 18: 973-84. 10.1016\/j.devcel.2010.05.009","journal-title":"Dev Cell"},{"key":"892_CR36","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/sj.cr.7290205","volume":"14","author":"DH Zhao","year":"2004","unstructured":"Zhao DH, Hong JJ, Guo SY, Yang RL, Yuan J, Wen CY, Zhou KY, Li CJ: Aberrant expression and function of TCF4 in the proliferation of hepatocellular carcinoma cell line BEL-7402. Cell Res 2004, 14: 74-80. 10.1038\/sj.cr.7290205","journal-title":"Cell Res"},{"key":"892_CR37","doi-asserted-by":"publisher","first-page":"2486","DOI":"10.1128\/MCB.01736-06","volume":"27","author":"D Malin","year":"2007","unstructured":"Malin D, Kim IM, Boetticher E, Kalin TV, Ramakrishna S, Meliton L, Ustiyan V, Zhu X, Kalinichenko VV: Forkhead box F1 is essential for migration of mesenchymal cells and directly induces integrin-beta3 expression. Mol Cell Biol 2007, 27: 2486-98. 10.1128\/MCB.01736-06","journal-title":"Mol Cell Biol"},{"key":"892_CR38","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1242\/dev.02252","volume":"133","author":"M Ormestad","year":"2006","unstructured":"Ormestad M, Astorga J, Landgren H, Wang T, Johansson BR, Miura N, Carlsson P: Foxf1 and Foxf2 control murine gut development by limiting mesenchymal Wnt signaling and promoting extracellular matrix production. Development 2006, 133: 833-43. 10.1242\/dev.02252","journal-title":"Development"},{"key":"892_CR39","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.tcb.2008.01.006","volume":"18","author":"V Gogvadze","year":"2008","unstructured":"Gogvadze V, Orrenius S, Zhivotovsky B: Mitochondria in cancer cells: what is so special about them? Trends Cell Biol 2008, 18: 165-73. 10.1016\/j.tcb.2008.01.006","journal-title":"Trends Cell Biol"},{"key":"892_CR40","first-page":"747","volume":"40","author":"J Zhang","year":"2012","unstructured":"Zhang J, Luo N, Luo Y, Peng Z, Zhang T, Li S: microRNA-150 inhibits human CD133-positive liver cancer stem cells through negative regulation of the transcription factor c-Myb. Int J Oncol 2012, 40: 747-756.","journal-title":"Int J Oncol"},{"key":"892_CR41","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1093\/carcin\/bgn195","volume":"29","author":"T Xu","year":"2008","unstructured":"Xu T, Zhu Y, Wei QK, Yuan Y, Zhou F, Ge YY, Yang JR, Su H, Zhuang SM: A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. Carcinogenesis 2008, 29: 2126-31. 10.1093\/carcin\/bgn195","journal-title":"Carcinogenesis"},{"key":"892_CR42","doi-asserted-by":"publisher","first-page":"18158","DOI":"10.1074\/jbc.M800186200","volume":"283","author":"S Kim","year":"2008","unstructured":"Kim S, Lee UJ, Kim MN, Lee EJ, Kim JY, Lee MY, Choung S, Kim YJ, Choi YC: MicroRNA miR-199a* regulates the MET proto-oncogene and the downstream extracellular signal-regulated kinase 2 (ERK2). J Biol Chem 2008, 283: 18158-66. 10.1074\/jbc.M800186200","journal-title":"J Biol Chem"},{"key":"892_CR43","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1158\/0008-5472.CAN-07-2488","volume":"68","author":"H Yang","year":"2008","unstructured":"Yang H, Kong W, He L, Zhao JJ, O'Donnell JD, Wang J, Wenham RM, Coppola D, Kruk PA, Nicosia SV, Cheng JQ: MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res 2008, 68: 425-33. 10.1158\/0008-5472.CAN-07-2488","journal-title":"Cancer Res"},{"key":"892_CR44","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1073\/pnas.0907904107","volume":"107","author":"P Pineau","year":"2010","unstructured":"Pineau P, Volinia S, McJunkin K, Marchio A, Battiston C, Terris B, Mazzaferro V, Lowe SW, Croce CM, Dejean A: miR-221 overexpression contributes to liver tumorigenesis. Proc Natl Acad Sci USA 2010, 107: 264-9. 10.1073\/pnas.0907904107","journal-title":"Proc Natl Acad Sci USA"},{"key":"892_CR45","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/S0303-7207(02)00096-5","volume":"193","author":"ND Maria","year":"2002","unstructured":"Maria ND, Manno M, Villa E: Sex hormones and liver cancer. Mol Cell Endocrinol 2002, 193: 59-63. 10.1016\/S0303-7207(02)00096-5","journal-title":"Mol Cell Endocrinol"},{"key":"892_CR46","doi-asserted-by":"publisher","first-page":"614","DOI":"10.2174\/138920008785821666","volume":"9","author":"S Kakizaki","year":"2008","unstructured":"Kakizaki S, Yamazaki Y, Takizawa D, Negishi M: New Insights on the Xenobiotic-Sensing Nuclear Receptors in Liver Diseases \u2013 CAR and PXR-. Curr Drug Metab 2008, 9: 614-621. 10.2174\/138920008785821666","journal-title":"Curr Drug Metab"},{"key":"892_CR47","doi-asserted-by":"publisher","first-page":"2001","DOI":"10.1053\/j.gastro.2006.02.030","volume":"130","author":"Y Zhai","year":"2006","unstructured":"Zhai Y, Zhou G, Deng G, Xie W, Dong X, Zhang X, Yu L, Yang H, Yuan X, Zhang H, Zhi L, Yao Z, Shen Y, Qiang B, He F: Estrogen receptor alpha polymorphisms associated with susceptibility to hepatocellular carcinoma in hepatitis B virus carriers. Gastroenterology 2006, 130: 2001-9. 10.1053\/j.gastro.2006.02.030","journal-title":"Gastroenterology"},{"key":"892_CR48","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/nrm714","volume":"3","author":"JM Trimarchi","year":"2002","unstructured":"Trimarchi JM, Lees JA: Sibling rivalry in the E2F family. Nat Rev Mol Cell Biol 2002, 3: 11-20.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"892_CR49","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1186\/1471-2105-11-419","volume":"11","author":"M Lu","year":"2010","unstructured":"Lu M, Shi B, Wang J, Cao Q, Cui Q: TAM: a method for enrichment and depletion analysis of a microRNA category in a list of microRNAs. BMC Bioinforma 2010, 11: 419. 10.1186\/1471-2105-11-419","journal-title":"BMC Bioinforma"},{"key":"892_CR50","doi-asserted-by":"publisher","first-page":"e3420","DOI":"10.1371\/journal.pone.0003420","volume":"3","author":"M Lu","year":"2008","unstructured":"Lu M, Zhang Q, Deng M, Miao J, Guo Y, Gao W, Cui Q: An analysis of human microRNA and disease associations. PLoS One 2008, 3: e3420. 10.1371\/journal.pone.0003420","journal-title":"PLoS One"},{"key":"892_CR51","doi-asserted-by":"publisher","first-page":"8852","DOI":"10.1158\/0008-5472.CAN-08-0517","volume":"68","author":"JT Park","year":"2008","unstructured":"Park JT, Shih IM, Wang TL: Identification of Pbx1, a potential oncogene, as a Notch3 target gene in ovarian cancer. Cancer Res 2008, 68: 8852-60. 10.1158\/0008-5472.CAN-08-0517","journal-title":"Cancer Res"},{"key":"892_CR52","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1002\/hep.23221","volume":"50","author":"MH Yang","year":"2009","unstructured":"Yang MH, Chen CL, Chau GY, Chiou SH, Su CW, Chou TY, Peng WL, Wu JC: Comprehensive analysis of the independent effect of twist and snail in promoting metastasis of hepatocellular carcinoma. Hepatology 2009, 50: 1464-74. 10.1002\/hep.23221","journal-title":"Hepatology"},{"key":"892_CR53","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1002\/hep.21592","volume":"45","author":"JM Pascussi","year":"2007","unstructured":"Pascussi JM, Robert A, Moreau A, Ramos J, Bioulac-Sage P, Navarro F, Blanc P, Assenat E, Maurel P, Vilarem MJ: Differential regulation of constitutive androstane receptor expression by hepatocyte nuclear factor4alpha isoforms. Hepatology 2007, 45: 1146-53. 10.1002\/hep.21592","journal-title":"Hepatology"},{"key":"892_CR54","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1038\/ng.370","volume":"41","author":"BS Carver","year":"2009","unstructured":"Carver BS, Tran J, Gopalan A, Chen Z, Shaikh S, Carracedo A, Alimonti A, Nardella C, Varmeh S, Scardino PT, Cordon-Cardo C, Gerald W, Pandolfi PP: Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate. Nat Genet 2009, 41: 619-24. 10.1038\/ng.370","journal-title":"Nat Genet"},{"key":"892_CR55","doi-asserted-by":"publisher","first-page":"e13344","DOI":"10.1371\/journal.pone.0013344","volume":"5","author":"F Lehner","year":"2010","unstructured":"Lehner F, Kulik U, Klempnauer J, Borlak J: Inhibition of the liver enriched protein FOXA2 recovers HNF6 activity in human colon carcinoma and liver hepatoma cells. PLoS One 2010, 5: e13344. 10.1371\/journal.pone.0013344","journal-title":"PLoS One"},{"key":"892_CR56","doi-asserted-by":"publisher","first-page":"101","DOI":"10.3892\/or_00000396","volume":"21","author":"SW Shin","year":"2009","unstructured":"Shin SW, Kwon HC, Rho MS, Choi HJ, Kwak JY, Park JI: Clinical significance of chicken ovalbumin upstream promoter-transcription factor II expression in human colorectal cancer. Oncol Rep 2009, 21: 101-6.","journal-title":"Oncol Rep"},{"key":"892_CR57","doi-asserted-by":"publisher","first-page":"25259","DOI":"10.1074\/jbc.M600466200","volume":"281","author":"SS Nakerakanti","year":"2006","unstructured":"Nakerakanti SS, Kapanadze B, Yamasaki M, Markiewicz M, Trojanowska M: Fli1 and Ets1 have distinct roles in connective tissue growth factor\/CCN2 gene regulation and induction of the profibrotic gene program. J Biol Chem 2006, 281: 25259-69. 10.1074\/jbc.M600466200","journal-title":"J Biol Chem"},{"key":"892_CR58","doi-asserted-by":"publisher","first-page":"3140","DOI":"10.1002\/jcb.23240","volume":"112","author":"D Zhang","year":"2011","unstructured":"Zhang D, Liu J, Wang Y, Chen J, Chen T: shRNA-mediated silencing of Gli2 gene inhibits proliferation and sensitizes human hepatocellular carcinoma cells towards TRAIL-induced apoptosis. J Cell Biochem 2011, 112: 3140-50. 10.1002\/jcb.23240","journal-title":"J Cell Biochem"},{"key":"892_CR59","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1186\/1471-2407-7-236","volume":"7","author":"P Bu","year":"2007","unstructured":"Bu P, Wan YJ: Fenretinide-induced apoptosis of Huh-7 hepatocellular carcinoma is retinoic acid receptor beta dependent. BMC cancer 2007, 7: 236. 10.1186\/1471-2407-7-236","journal-title":"BMC cancer"},{"key":"892_CR60","doi-asserted-by":"publisher","first-page":"491","DOI":"10.3892\/ijmm.2011.600","volume":"27","author":"Y Wu","year":"2011","unstructured":"Wu Y, Sato F, Bhawal UK, Kawamoto T, Fujimoto K, Noshiro M, Morohashi S, Kato Y, Kijima H: Basic helix-loop-helix transcription factors DEC1 and DEC2 regulate the paclitaxel-induced apoptotic pathway of MCF-7 human breast cancer cells. Int J Mol Med 2011, 27: 491-5.","journal-title":"Int J Mol Med"},{"key":"892_CR61","doi-asserted-by":"publisher","first-page":"8581","DOI":"10.1128\/MCB.25.19.8581-8591.2005","volume":"25","author":"J Pratap","year":"2005","unstructured":"Pratap J, Javed A, Languino LR, van Wijnen AJ, Stein JL, Stein GS, Lian JB: The Runx2 osteogenic transcription factor regulates matrix metalloproteinase 9 in bone metastatic cancer cells and controls cell invasion. Mol Cell Biol 2005, 25: 8581-91. 10.1128\/MCB.25.19.8581-8591.2005","journal-title":"Mol Cell Biol"},{"key":"892_CR62","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1517\/14728222.11.4.507","volume":"11","author":"H Nakshatri","year":"2007","unstructured":"Nakshatri H, Badve S: FOXA1 as a therapeutic target for breast cancer. Expert Opin Ther Targets 2007, 11: 507-14. 10.1517\/14728222.11.4.507","journal-title":"Expert Opin Ther Targets"},{"key":"892_CR63","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.jhep.2010.02.021","volume":"53","author":"C Liu","year":"2010","unstructured":"Liu C, Yu J, Yu S, Lavker RM, Cai L, Liu W, Yang K, He X, Chen S: MicroRNA-21 acts as an oncomir through multiple targets in human hepatocellular carcinoma. J Hepatol 2010, 53: 98-107. 10.1016\/j.jhep.2010.02.021","journal-title":"J Hepatol"},{"key":"892_CR64","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1002\/hep.23100","volume":"50","author":"B Wang","year":"2009","unstructured":"Wang B, Majumder S, Nuovo G, Kutay H, Volinia S, Patel T, Schmittgen TD, Croce C, Ghoshal K, Jacob ST: Role of microRNA-155 at early stages of hepatocarcinogenesis induced by choline-deficient and amino acid-defined diet in C57BL\/6 mice. Hepatology 2009, 50: 1152-61. 10.1002\/hep.23100","journal-title":"Hepatology"},{"key":"892_CR65","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1016\/j.febslet.2011.03.067","volume":"585","author":"L Wu","year":"2011","unstructured":"Wu L, Cai C, Wang X, Liu M, Li X, Tang H: MicroRNA-142-3p, a new regulator of RAC1, suppresses the migration and invasion of hepatocellular carcinoma cells. FEBS Lett 2011, 585: 1322-30. 10.1016\/j.febslet.2011.03.067","journal-title":"FEBS Lett"},{"key":"892_CR66","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.surg.2010.05.007","volume":"148","author":"SD Bhattacharya","year":"2010","unstructured":"Bhattacharya SD, Garrison J, Guo H, Mi Z, Markovic J, Kim VM, Kuo PC: Micro-RNA-181a regulates osteopontin-dependent metastatic function in hepatocellular cancer cell lines. Surgery 2010, 148: 291-7. 10.1016\/j.surg.2010.05.007","journal-title":"Surgery"},{"key":"892_CR67","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1038\/nrc2222","volume":"7","author":"JA Menendez","year":"2007","unstructured":"Menendez JA, Lupu R: Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer 2007, 7: 763-77. 10.1038\/nrc2222","journal-title":"Nat Rev Cancer"},{"key":"892_CR68","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1101\/gr.229102. Article published online before print in May 2002","volume":"12","author":"WJ Kent","year":"2002","unstructured":"Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, Haussler D: The Human Genome Browser at UCSC. Genome Res 2002, 12: 996-1006.","journal-title":"Genome Res"},{"key":"892_CR69","doi-asserted-by":"publisher","first-page":"D108","DOI":"10.1093\/nar\/gkj143","volume":"34","author":"V Matys","year":"2006","unstructured":"Matys V, Kel-Margoulis OV, Fricke E, Liebich I, Land S, Barre-Dirrie A, Reuter I, Chekmenev D, Krull M, Hornischer K, Voss N, Stegmaier P, Lewicki-Potapov B, Saxel H, Kel AE, Wingender E: TRANSFAC and its module TRANSCompel: transcriptional gene regulation in eukaryotes. Nucleic Acids Res 2006, 34: D108-10. 10.1093\/nar\/gkj143","journal-title":"Nucleic Acids Res"},{"key":"892_CR70","doi-asserted-by":"publisher","first-page":"3576","DOI":"10.1093\/nar\/gkg585","volume":"31","author":"AE Kel","year":"2003","unstructured":"Kel AE, G\u00f6ssling E, Reuter I, Cheremushkin E, Kel-Margoulis OV, Wingender E: MATCHTM: a tool for searching transcription factor binding sites in DNA sequences. Nucleic Acids Res 2003, 31: 3576-3579. 10.1093\/nar\/gkg585","journal-title":"Nucleic Acids Res"},{"key":"892_CR71","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.cell.2004.12.035","volume":"120","author":"BP Lewis","year":"2005","unstructured":"Lewis BP, Burge CB, Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005, 120: 15-20. 10.1016\/j.cell.2004.12.035","journal-title":"Cell"},{"key":"892_CR72","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nprot.2008.211","volume":"4","author":"DW Huang","year":"2009","unstructured":"Huang DW, Sherman BT, Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009, 4: 44-57.","journal-title":"Nat Protoc"},{"key":"892_CR73","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","volume":"57","author":"Y Benjamini","year":"1995","unstructured":"Benjamini Y, Hochberg Y: Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. Journal of the Royal Statistical Society. Series B (Methodological) 1995, 57: 289.","journal-title":"Journal of the Royal Statistical Society. Series B (Methodological)"},{"key":"892_CR74","volume-title":"InterJournal","author":"G Csardi","year":"2006","unstructured":"Csardi G, Nepusz T: The igraph software package for complex network research. InterJournal 2006. Complex Systems No. 1695"},{"key":"892_CR75","doi-asserted-by":"publisher","first-page":"2366","DOI":"10.1038\/nprot.2007.324","volume":"2","author":"MS Cline","year":"2007","unstructured":"Cline MS, Smoot M, Cerami E, Kuchinsky A, Landys N, Workman C, Christmas R, Avila-Campilo I, Creech M, Gross B, Hanspers K, Isserlin R, Kelley R, Killcoyne S, Lotia S, Maere S, Morris J, Ono K, Pavlovic V, Pico AR, Vailaya A, Wang PL, Adler A, Conklin BR, Hood L, Kuiper M, Sander C, Schmulevich I, Schwikowski B, Warner GJ, Ideker T, Bader GD: Integration of biological networks and gene expression data using Cytoscape. Nat Protoc 2007, 2: 2366-82. 10.1038\/nprot.2007.324","journal-title":"Nat Protoc"}],"container-title":["BMC Systems Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1752-0509-6-32.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T19:17:59Z","timestamp":1630523879000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcsystbiol.biomedcentral.com\/articles\/10.1186\/1752-0509-6-32"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,5,1]]},"references-count":75,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,12]]}},"alternative-id":["892"],"URL":"https:\/\/doi.org\/10.1186\/1752-0509-6-32","relation":{},"ISSN":["1752-0509"],"issn-type":[{"value":"1752-0509","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,5,1]]},"assertion":[{"value":"14 February 2012","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 May 2012","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 May 2012","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"32"}}