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While previous work has primarily focussed on understanding the direct and indirect mechanisms of Hepatitis B virus X protein (HBx)\u2010mediated hepatocarcinogenesis, from genetic and epigenetic perspectives, its influence on RNA modification mediated onset of liver malignancies is less well understood. This study explored the role of HBV\u2010encoded HBx in altering the m6A methylome profile and its implications on the pathogenesis of HCC. We established HBx\u2010expressing stable HCC cell lines, Huh7\u2010HBx and HepG2\u2010HBx, and explored the transcriptomic and epitranscriptomic profiles by RNA\u2010seq and MeRIP\u2010seq, respectively. Preliminary results suggest that HBx promotes liver cell proliferation, migration, survival and overall m6A methylation in HCC cells and is involved in modulating the extracellular matrix. We show that HBx mediates liver cell transformation by upregulating KIAA1429 methyltransferase. HBx also drives the expression and hypermethylation of the extracellular matrix protein HSPG2\/Perlecan and promotes tumourigenesis. Furthermore, we observed a potential interaction between KIAA1429 and HSPG2 in HCC liver cancer cells and demands further investigation.<\/jats:p>","DOI":"10.1002\/mc.23830","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T14:09:40Z","timestamp":1729519780000},"page":"108-125","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Hepatitis B Virus X Protein Contributes to Hepatocellular Carcinoma via Upregulation of KIAA1429 Methyltransferase and mRNA m6A Hypermethylation of HSPG2\/Perlecan"],"prefix":"10.1002","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6078-7190","authenticated-orcid":false,"given":"Enakshi","family":"Sivasudhan","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, School of Science Xi'an Jiaotong\u2014Liverpool University Suzhou China"},{"name":"Suzhou Municipal Key Lab of Cancer Biology and Chronic Disease, School of Science Xi'an Jiaotong\u2014Liverpool University Suzhou China"},{"name":"Department of Clinical Infection, Microbiology and Immunology, Institute of Infection, Veterinary and Ecological Sciences University of Liverpool Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingxian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Suzhou Municipal Key Lab of Cancer Biology and Chronic Disease, School of Science Xi'an Jiaotong\u2014Liverpool University Suzhou China"},{"name":"School of AI and Advanced Computing Xi'an Jiaotong\u2014Liverpool University Suzhou China"},{"name":"Department of Computer Science University of Liverpool Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiongming","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Science Xi'an Jiaotong\u2014Liverpool University Suzhou China"},{"name":"Suzhou Municipal Key Lab of Cancer Biology and Chronic Disease, School of Science Xi'an Jiaotong\u2014Liverpool University Suzhou China"},{"name":"Institute of Systems, Molecular and Integrative Biology University of Liverpool Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Science Xi'an Jiaotong\u2014Liverpool University Suzhou China"},{"name":"Suzhou Municipal Key Lab of Cancer Biology and Chronic Disease, School of Science Xi'an Jiaotong\u2014Liverpool University Suzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Science Xi'an Jiaotong\u2014Liverpool University Suzhou China"},{"name":"Suzhou Municipal Key Lab of Cancer Biology and Chronic Disease, School of Science Xi'an Jiaotong\u2014Liverpool University Suzhou China"},{"name":"Chinese Academy of Medical Sciences &amp; 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