{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:48:49Z","timestamp":1788929329649,"version":"build-2803163510"},"reference-count":41,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Hepatitis B virus (HBV) precore G1896A mutation is closely associated with poor prognosis of liver disease. We previously revealed that the G1896A mutation could enhance HBV replication and promote hepatocellular carcinoma (HCC) cell growth both in vitro and in vivo. However, the in\u2010depth mechanisms by which this mutation promotes the malignancy of HCC still need to be explored. Here, we examined the activation of endoplasmic reticulum (ER) stress and glycolysis in HBV G1896A mutation\u2013associated HCC. Bioinformatics, chromatin immunoprecipitation assay and dual\u2010luciferase assay were performed to give insight into the underlying molecular interaction between ER stress and glycolysis. Here, we observed that HBV G1896A mutation also promoted HCC cell invasion and migration. Furthermore, HBV G1896A mutation induced ER stress, and specifically, PERK\u2010ATF4 pathway was responsible for the HCC cell malignancy. Mechanistically, PERK\u2010ATF4 signaling induced transcriptional activation of PFKFB3, a key gene in the process of glycolysis. Finally, in vitro rescue experiments and in vivo efficacy studies revealed that the ATF4\u2010PFKFB3 axis is necessary for the HCC tumor growth and metastasis. These results highlight that the ER stress and glycolysis are involved in the HCC\u2010promotion function of HBV G1896A mutation, providing new insights into HBV\u2010related HCC.<\/jats:p>","DOI":"10.1002\/mco2.70365","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T06:42:10Z","timestamp":1756968130000},"source":"Crossref","is-referenced-by-count":2,"title":["HBV Precore G1896A Mutation Promotes Malignancy of Hepatocellular Carcinoma by Activating Endoplasmic Reticulum Stress to Enhance Aerobic Glycolysis"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4993-3042","authenticated-orcid":false,"given":"Baoxin","family":"Zhao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety Wuhan Institute of Virology Center For Biosafety Mega Science Chinese Academy of Sciences  Wuhan Hubei China"},{"name":"Department of Pathogen Biology Hebei Medical University  Shijiazhuang Hebei 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