{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:57:27Z","timestamp":1791385047172,"version":"4.3.3"},"reference-count":50,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The interaction between Hepatitis B virus X protein (HBx) and sterol regulatory element binding protein 2 (SREBP2) in modulating autophagy to influence inflammation and tumorigenesis is not fully understood. This research seeks to clarify the regulatory role of HBx in hepatocyte autophagy through SREBP2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study employed TCGA and GEO databases to investigate the expression of SREBF2 and autophagy\u2010related proteins in liver cancer. Various experimental techniques, including dual\u2010luciferase reporter assays, immunohistochemistry, Western blotting, immunofluorescence, GFP\u2010mRFP\u2010LC3 puncta analysis, transmission electron microscopy, and Fillipin III staining, were conducted on HBV\u2010associated liver cancer tissues, HBV transgenic mice, and several liver cancer cell lines to assess the levels of HBx, SREBP2, autophagy, and cholesterol, respectively, as well as to explore potential associations between these factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Bioinformatics analysis suggested up\u2010regulation of SREBP2 and autophagy\u2010associated genes in HBV\u2010associated liver cancer. Elevated levels of cholesterol, SREBP2, and autophagy flux were detected in HBV\u2010associated liver cancer tissues as compared to adjacent tissues. HBV transgenic mice had higher cholesterol, SREBP2, and autophagy levels than wild\u2010type mice. HBx activated the SREBP2 promoter to enhance its transcription and nuclear translocation. HBx knockdown down\u2010regulated SREBP2 expression and nuclear translocation levels in HepG2.2.15\u2010siHBx cells. HepG2.2.15 and HepG2\u2010HBx showed more autolysosomes than HepG2 cells; furthermore, HepG2.2.15\u2010siHBx cells had fewer autolysosomes than HepG2.2.15 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This research highlights that HBx upregulates SREBP2 and increases autophagic flux, accompanied by changes in cholesterol metabolism, which offers an additional theoretical foundation to elucidate that chronic HBV infection causes abnormal lipid metabolism and induces tumorigenesis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.70916","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T10:43:43Z","timestamp":1749206623000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Hepatitis B Virus X Protein Upregulates <scp>SREBP2<\/scp> to Modulate Autophagy in Hepatocellular 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