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As an important hepatitis B virus (HBV) oncoprotein, pre\u2010S2 mutant activates multiple signalling pathways to induce HCC development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study investigated the effect of pre\u2010S2 mutant on regulating microRNA (miRNA) expression and the role of miRNAs in mediating pre\u2010S2 mutant's oncogenic functions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The results showed that 9 miRNAs were downregulated in both tumour tissues of pre\u2010S2 mutant\u2010positive HCC patients and pre\u2010S2 mutant\u2010expressed human HCC cell lines, contributing to pre\u2010S2 mutant\u2010promoted cell proliferation, anchorage\u2010independent cell growth, cell cycle progression, and tumour growth and malignancy. Moreover, pre\u2010S2 mutant downregulated miRNA expression at the epigenetic levels through suppression of lysine acetyltransferase 3B (KAT3B)\u2010 and KAT5\u2010mediated histone H3 lysine 9 acetylation (H3K9ac) and H4K5ac modifications. The decreased levels of pre\u2010S2 mutant\u2010dysregulated miRNAs could also be detected in blood exosomes of patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Collectively, this study provided new mechanistic insights and therapeutic perspectives for pre\u2010S2 mutant\u2010associated HCC tumorigenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70582","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T06:55:38Z","timestamp":1773039338000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Epigenetic Regulation of MicroRNA Expression by Hepatitis B Virus Pre\u2010S2 Mutant Promotes Hepatocellular Carcinoma 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