{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T04:23:14Z","timestamp":1769314994399,"version":"3.49.0"},"reference-count":69,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,11,28]],"date-time":"2019-11-28T00:00:00Z","timestamp":1574899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health and Welfare","award":["108-0324-01-19-07"],"award-info":[{"award-number":["108-0324-01-19-07"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The primary type of liver cancer, hepatocellular carcinoma (HCC), has been associated with nonalcoholic steatohepatitis, diabetes, and obesity. Previous studies have identified some genetic risk factors, such as hepatitis B virus X antigens, overexpression of SRC oncogene, and mutation of the p53 tumor suppressor gene; however, the synergism between diet and genetic risk factors is still unclear. To investigate the synergism between diet and genetic risk factors in hepatocarcinogenesis, we used zebrafish with four genetic backgrounds and overfeeding or high-fat-diet-induced obesity with an omics-based expression of genes and histopathological changes. The results show that overfeeding and high-fat diet can induce obesity and nonalcoholic steatohepatitis in wild-type fish. In HBx, Src (p53-) triple transgenic zebrafish, diet-induced obesity accelerated HCC formation at five months of age and increased the cancer incidence threefold. We developed a global omics data analysis method to investigate genes, pathways, and biological systems based on microarray and next-generation sequencing (NGS, RNA-seq) omics data of zebrafish with four diet and genetic risk factors. The results show that two Kyoto Encyclopedia of Genes and Genomes (KEGG) systems, metabolism and genetic information processing, as well as the pathways of fatty acid metabolism, steroid biosynthesis, and ribosome biogenesis, are activated during hepatocarcinogenesis. This study provides a systematic view of the synergism between genetic and diet factors in the dynamic liver cancer formation process, and indicate that overfeeding or a high-fat diet and the risk genes have a synergistic effect in causing liver cancer by affecting fatty acid metabolism and ribosome biogenesis.<\/jats:p>","DOI":"10.3390\/cancers11121899","type":"journal-article","created":{"date-parts":[[2019,11,28]],"date-time":"2019-11-28T10:54:10Z","timestamp":1574938450000},"page":"1899","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Omics-based Investigation of Diet-induced Obesity Synergized with HBx, Src, and p53 Mutation Accelerating Hepatocarcinogenesis in Zebrafish Model"],"prefix":"10.3390","volume":"11","author":[{"given":"Wan-Yu","family":"Yang","sequence":"first","affiliation":[{"name":"Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan 35053, Miaoli, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei-Shu","family":"Rao","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan 35053, Miaoli, Taiwan"},{"name":"Department of Life Science, National Tsing-Hua University, Hsinchu 30070, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5611-542X","authenticated-orcid":false,"given":"Yong-Chun","family":"Luo","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu 30010, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua-Kuo","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan 35053, Miaoli, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0289-2260","authenticated-orcid":false,"given":"Sing-Han","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu 30010, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinn-Moon","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu 30010, Taiwan"},{"name":"Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30010, Taiwan"},{"name":"Center for Intelligent Drug Systems and Smart Bio-devices, National Chiao Tung University, Hsinchu 30010, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2356-1551","authenticated-orcid":false,"given":"Chiou-Hwa","family":"Yuh","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan 35053, Miaoli, Taiwan"},{"name":"Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30010, Taiwan"},{"name":"Institute of Bioinformatics and Structural Biology, National Tsing-Hua University, Hsinchu 30070, Taiwan"},{"name":"Program in Environmental and Occupational Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1055\/s-2005-871200","article-title":"Hepatocellular carcinoma: Molecular pathways and new therapeutic targets","volume":"25","author":"Roberts","year":"2005","journal-title":"Semin. 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