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Our previous studies indicate that the hedgehog signalling is involved in hepatic carcinogenesis, metastasis and chemo\u2010resistance. The present study aims to uncover molecular mechanisms underlying hepatoma chemo\u2010resistance. TAP1 and GLI1\/2 gene expression was assessed in both poorly differentiated hepatoma cells and HCC specimens. Potential GLI\u2010binding site in the TAP1 promoter sequence was validated by molecular assays. Approximately 75% HCC specimens exhibited an elevated expression of hedgehog GLI1 transcription factor compared with adjacent liver tissue. Both GLI1\/2 and TAP1 protein levels were significantly elevated in poorly differentiated hepatoma cells. Both Huh\u20107\u2010trans and Huh\u20107\u2010DN displayed more karyotypic abnormalities and differential gene expression profiles than their native Huh\u20107 cells. Sensitivity to Sorafenib, doxorubicin and cisplatin was remarkably improved after either GLI1 or TAP1 gene was inhibited by an RNAi approach or by a specific GLI1\/2 inhibitor, GANT61. Further experiments confirmed that hedgehog transcription factor GLI1\/2 binds to the TAP1 promoter, indicating that TAP1 is one of GLI1\/2 target genes. In conclusion, TAP1 is under direct transcriptional control of the hedgehog signalling. Targeting hedgehog signalling confers a novel insight into alleviating drug resistance in the treatment of refractory HCC.<\/jats:p>","DOI":"10.1111\/jcmm.15090","type":"journal-article","created":{"date-parts":[[2020,2,28]],"date-time":"2020-02-28T09:10:01Z","timestamp":1582881001000},"page":"4298-4311","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Hedgehog signalling mediates drug resistance through targeting TAP1 in hepatocellular carcinoma"],"prefix":"10.1111","volume":"24","author":[{"given":"Xiao\u2010Tian","family":"Zhou","sequence":"first","affiliation":[{"name":"MOE\/NHC\/CAMS Key Laboratory of Medical Molecular Virology Department of Medical Microbiology and Parasitology School of Basic Medical Sciences Shanghai Medical College Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7391-8520","authenticated-orcid":false,"given":"Jia","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai Jing'an District Central Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui\u2010Yan","family":"Li","sequence":"additional","affiliation":[{"name":"MOE\/NHC\/CAMS Key Laboratory of Medical Molecular Virology Department of Medical Microbiology and Parasitology School of Basic Medical Sciences Shanghai Medical College Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie\u2010Liang","family":"Zuo","sequence":"additional","affiliation":[{"name":"Department of General Surgery Huashan Hospital of Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng\u2010Yang","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of General Surgery Huashan Hospital of Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu\u2010Liang","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of General Surgery Huashan Hospital of Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9933-7364","authenticated-orcid":false,"given":"Jian","family":"Wu","sequence":"additional","affiliation":[{"name":"MOE\/NHC\/CAMS Key Laboratory of Medical Molecular Virology Department of Medical Microbiology and Parasitology School of Basic Medical Sciences Shanghai Medical College Fudan University Shanghai China"},{"name":"Department of Gastroenterology &amp; 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