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Hepatocellular carcinoma (HCC) is one of the most common inflammation-associated cancers; most HCCs arise in the setting of chronic inflammation and hepatic injury. Both NF-\u03baB and STAT3 are important regulators of inflammation. Centrosomal P4.1-associated protein (CPAP), a centrosomal protein that participates primarily in centrosome functions, is overexpressed in HCC and can increase TNF-\u03b1-mediated NF-\u03baB activation and IL-6-induced STAT3 activation. A transgenic (Tg) mouse model with hepatocyte-specific CPAP expression was established to investigate the physiological role of CPAP in hepatocarcinogenesis. Obvious inflammatory cell accumulation and fatty change were observed in the livers of <jats:italic>CPAP<\/jats:italic> Tg mice. The alanine aminotransferase (ALT) level and the expression levels of inflammatory genes, such as IL-6, IL-1\u03b2 and TNF-\u03b1, were higher in <jats:italic>CPAP<\/jats:italic> Tg mice than in wild type (WT) mice. High-dose\/short-term treatment with diethylnitrosamine (DEN) increased the ALT level, proinflammatory gene expression levels, and STAT3 and NF-\u03baB activation in <jats:italic>CPAP<\/jats:italic> Tg mice; low-dose\/long-term DEN treatment induced more severe liver tumor formation in <jats:italic>CPAP<\/jats:italic> Tg mice than in WT mice. CPAP can increase the expression of chemokine (C-C motif) ligand 16 (CCL-16), an important chemotactic cytokine, in human hepatocytes. CCL-16 expression is positively correlated with <jats:italic>CPAP<\/jats:italic> and <jats:italic>TNF-\u03b1<\/jats:italic> mRNA expression in the peritumoral part of HCC. In summary, these results suggest that CPAP may promote hepatocarcinogenesis through enhancing the inflammation pathway via increasing the expression of CCL-16.<\/jats:p>","DOI":"10.1038\/s41419-021-04295-2","type":"journal-article","created":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T12:02:55Z","timestamp":1634904175000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["CPAP enhances and maintains chronic inflammation in hepatocytes to promote hepatocarcinogenesis"],"prefix":"10.1038","volume":"12","author":[{"given":"Ruo-Yu","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Jui","family":"Yen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yih-Jyh","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju-Ming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Fen","family":"Tasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chuan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-Wen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Wen","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Hao","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7284-2608","authenticated-orcid":false,"given":"Liang-Yi","family":"Hung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,22]]},"reference":[{"key":"4295_CR1","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1038\/s41575-019-0186-y","volume":"16","author":"JD Yang","year":"2019","unstructured":"Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. 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