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However, the genetic alterations and pathogenesis mechanisms remain significantly unexplored, especially for HBV-induced metabolic reprogramming. Analysis of integration breakpoints in HBV-positive HCC samples revealed the preferential clustering pattern within the 3\u2032-end of X gene in the HBV genome, leading to the production of C-terminal truncated X protein (Ct-HBx). In this study, we not only characterized the oncogenic role of two Ct-HBx (HBx-120 and HBx-134) via in vitro and in vivo functional assays but also deciphered their underlying molecular mechanisms. Gene expression profiling by transcriptome sequencing identified potential targets of Ct-HBx and novel malignant hallmarks such as glycolysis, cell cycle, and m-TORC1 signaling in Ct-HBx-expressing cells. TXNIP, a well-established regulator of glucose metabolism, was shown to be downregulated by Ct-HBx and play a pivotal role in Ct-HBx-mediated HCC progression. Suppression of TXNIP is frequently observed in HCC patients with Ct-HBx expression and significantly (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.015) correlated to a poorer prognosis. Re-introduction of TXNIP attenuated the metabolic reprogramming induced by the Ct-HBx and inhibited the tumor growth in the mice model. Further study suggested that Ct-HBx could downregulate TXNIP via a transcriptional repressor nuclear factor of activated T cells 2 (NFACT2). Collectively, our findings indicate that TXNIP plays a critical role in Ct-HBx-mediated hepatocarcinogenesis, serving as a novel therapeutic strategy in HCC treatment.\n                  <\/jats:p>","DOI":"10.1038\/s41388-020-01593-5","type":"journal-article","created":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T03:45:11Z","timestamp":1609818311000},"page":"1147-1161","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["C-terminal truncated HBx initiates hepatocarcinogenesis by downregulating TXNIP and reprogramming glucose metabolism"],"prefix":"10.1038","volume":"40","author":[{"given":"Yu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanqi","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beilei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaona","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching Ngar","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaojie","family":"Lyu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pak Chung","family":"Sham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4485-6017","authenticated-orcid":false,"given":"Xin-Yuan","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,12,15]]},"reference":[{"key":"1593_CR1","doi-asserted-by":"publisher","first-page":"2893","DOI":"10.1002\/ijc.25516","volume":"127","author":"J Ferlay","year":"2010","unstructured":"Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. 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