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KEGG pathway enrichment further implicated metabolic pathways in ME\u2010induced HCC development. Integration of STRING and Cytoscape analyses identified 14 hub targets, including key proteins such as <jats:italic>AURKB<\/jats:italic>, <jats:italic>CCNB1<\/jats:italic>, <jats:italic>CDK1<\/jats:italic>, and <jats:italic>PLK1<\/jats:italic>. Molecular docking studies demonstrated weak binding affinities of ME to these targets compared to their specific inhibitors. However, microarray data and survival analyses of human HCC samples revealed that <jats:italic>AURKB<\/jats:italic>, <jats:italic>CCNB1<\/jats:italic>, <jats:italic>CDK1<\/jats:italic>, and <jats:italic>PLK1<\/jats:italic> are upregulated in HCC, with higher expression levels correlating with poorer overall survival, particularly for <jats:italic>CCNB1<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings suggest that ME exposure may enhance the expression of these genes in hepatocytes, disrupting the cell cycle and promoting proliferation. This study provides valuable insights into the molecular mechanisms of ME\u2010induced HCC in humans and highlights potential therapeutic targets, such as <jats:italic>CCNB1<\/jats:italic>, for further investigation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.70768","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T07:36:03Z","timestamp":1747294563000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["In Silico Network Toxicology, Molecular Docking, and Multi\u2010Level Bioinformatics Reveal Methyl Eugenol\u2010Induced Hepatocellular Carcinoma Mechanisms in Humans"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5260-3650","authenticated-orcid":false,"given":"Fuat","family":"Karaku\u015f","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Toxicology Faculty of Pharmacy, Van Yuzuncu Yil University  Van Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z\u00fcbeyde","family":"Tanr\u0131verdi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Toxicology Faculty of Pharmacy, A\u011fr\u0131 \u0130brahim \u00c7e\u00e7en University  A\u011fr\u0131 Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burak","family":"Kuzu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Faculty of Pharmacy, Van Yuzuncu Yil University  Van Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/foods10092139"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/plants12112075"},{"key":"e_1_2_9_4_1","first-page":"517","article-title":"Aspartame, Methyleugenol, and Isoeugenol","volume":"134","author":"IARC Working Group on the Identification of Carcinogenic Hazards to Humans","year":"2023","journal-title":"IARC Monographs on the Evaluation of Carcinogenic Risks to Humans"},{"key":"e_1_2_9_5_1","first-page":"1","article-title":"NTP Toxicology and Carcinogenesis Studies of Methyleugenol (CAS NO. 93\u201315\u20102) in F344\/N Rats and B6C3F1 Mice (Gavage Studies)","volume":"491","author":"National Toxicology Program","year":"2000","journal-title":"National Toxicology Program Technical Report Series"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/14356007.t11_t02"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf000364a"},{"issue":"3","key":"e_1_2_9_8_1","first-page":"1124","article-title":"Structure\u2010Activity Studies of the Carcinogenicities in the Mouse and Rat of Some Naturally Occurring and Synthetic Alkenylbenzene Derivatives Related to Safrole and Estragole","volume":"43","author":"Miller E. 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