{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T22:49:03Z","timestamp":1785883743195,"version":"3.56.0"},"reference-count":50,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,10,4]],"date-time":"2018-10-04T00:00:00Z","timestamp":1538611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["91529305"],"award-info":[{"award-number":["91529305"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81370527"],"award-info":[{"award-number":["81370527"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81702647"],"award-info":[{"award-number":["81702647"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2015HZ005"],"award-info":[{"award-number":["ZR2015HZ005"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR201702190483"],"award-info":[{"award-number":["ZR201702190483"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2016HB16"],"award-info":[{"award-number":["ZR2016HB16"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2018,12,15]]},"abstract":"<jats:p>Initiation of hepatocellular carcinoma (HCC) by chronic hepatitis B virus (HBV) infection is a complex process that includes both oncogene activation and tumor suppressor inhibition. The HBV X (HBx) protein has an important and complex role in processes leading to HCC. We previously identified the mammalian <jats:italic>Zinc fingers and homeoboxes 2<\/jats:italic> (<jats:italic>ZHX2<\/jats:italic>) gene as an HCC\u2010associated tumor suppressor gene. In the present study, we investigated whether the oncogenic properties of HBV and, more specifically, HBx, involved ZHX2 silencing. Our data indicates that ZHX2 expression is significantly decreased in tumor tissues from HBV\u2010positive HCC patients and livers from HBV transgenic mice. <jats:italic>In vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> studies confirmed that HBV\u2010encoded proteins, particularly HBx, inhibits both the expression and tumor suppression properties of ZHX2. Further analyses identified miR\u2010155, a well\u2010known oncomiR in various cancers, as an important link between HBx and ZHX2 inhibition. Increased miR\u2010155 levels were found in HBV\u2010positive tumors, livers of HBV transgenic mice and HBx\u2010overexpressing hepatoma cell lines. MiR\u2010155 overexpression reduced ZHX2 levels via miR\u2010155 seed sites in the ZHX2 3\u2032UTR, whereas blocking miR\u2010155 levels led to increased ZHX2 levels. Taken together, our data indicate that HCC\u2010promoting properties of HBV may include ZHX2 silencing via a miR\u2010155 dependent pathway and suggests a novel therapy for HBV\u2010related HCC.<\/jats:p>","DOI":"10.1002\/ijc.31595","type":"journal-article","created":{"date-parts":[[2018,5,12]],"date-time":"2018-05-12T05:29:51Z","timestamp":1526102991000},"page":"3120-3130","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["HBV suppresses ZHX2 expression to promote proliferation of HCC through miR\u2010155 activation"],"prefix":"10.1002","volume":"143","author":[{"given":"Xiaojia","family":"Song","sequence":"first","affiliation":[{"name":"Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology Shandong University School of Basic Medical Science  Jinan Shandong, 250012 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Tan","sequence":"additional","affiliation":[{"name":"Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology Shandong University School of Basic Medical Science  Jinan Shandong, 250012 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuanchang","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology Shandong University School of Basic Medical Science  Jinan Shandong, 250012 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leiqi","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology Shandong University School of Basic Medical Science  Jinan Shandong, 250012 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehua","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology Shandong University School of Basic Medical Science  Jinan Shandong, 250012 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology Shandong University School of Basic Medical Science  Jinan Shandong, 250012 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tixiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology Shandong University School of Basic Medical Science  Jinan Shandong, 250012 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengjiang","family":"Gao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Sciences Shandong University  Jinan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoqin","family":"Gong","sequence":"additional","affiliation":[{"name":"Key Laboratory for Experimental Teratology of Ministry of Education and Department of Genetics Shandong University School of Basic Medical Science  Jinan Shandong, 250012 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Liang","sequence":"additional","affiliation":[{"name":"Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology Shandong University School of Basic Medical Science  Jinan Shandong, 250012 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifen","family":"Gao","sequence":"additional","affiliation":[{"name":"Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology Shandong University School of Basic Medical Science  Jinan Shandong, 250012 People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett T.","family":"Spear","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics  Lexington KY"},{"name":"Markey Cancer Center, University of Kentucky College of Medicine  Lexington KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8121-4718","authenticated-orcid":false,"given":"Chunhong","family":"Ma","sequence":"additional","affiliation":[{"name":"Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology Shandong University School of Basic Medical Science  Jinan Shandong, 250012 People's Republic of China"},{"name":"Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Sciences Shandong University  Jinan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,4]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.03.011"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21161"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21262"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.30547"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12992"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i38.10732"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2008.174029"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2016.82"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2016.05.006"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-14-721"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2003.09.013"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20030171"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0408555102"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21825"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2008.00233.x"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2014.08.021"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.2741\/3483"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.02.049"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.2832"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1309\/09B452V7R76K7D6K"},{"key":"e_1_2_6_22_1","first-page":"207","article-title":"Expression of zinc\u2010fingers and homeoboxes 2 in hepatocellular carcinogenesis: a tissue microarray and clinicopathological analysis","volume":"54","author":"Hu S","year":"2007","journal-title":"Neoplasma"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2007.06956.x"},{"key":"e_1_2_6_24_1","first-page":"2140","article-title":"Microarray expression profiling identifies genes, including cytokines, and biofunctions, as diapedesis, associated with a brain metastasis from a papillary thyroid carcinoma","volume":"6","author":"Schulten HJ","year":"2016","journal-title":"Am J Cancer Res"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2015.2855"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20920"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90770-8"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.00049"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2008.144"},{"key":"e_1_2_6_30_1","first-page":"717","article-title":"Effect of preS2 antisense RNA on hepatocellular carcinoma with a novel delivery system","volume":"116","author":"Ma C","year":"2003","journal-title":"Chin Med J"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2017.87"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/286533a0"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3449"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.02.021"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.15"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2013-306228"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2016.177"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29316"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/v9080230"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.322"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.15183"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12090"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.109.902320"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2013.07.003"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2011.01.001"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.2.11.1427"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2011.10.019"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0171036"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2017.291"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-11-189845"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23100"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.31595","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.31595","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T04:06:48Z","timestamp":1694318808000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.31595"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,4]]},"references-count":50,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2018,12,15]]}},"alternative-id":["10.1002\/ijc.31595"],"URL":"https:\/\/doi.org\/10.1002\/ijc.31595","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,4]]},"assertion":[{"value":"2018-02-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}