Dietary cholesterol promotes steatohepatitis related hepatocellular carcinoma through dysregulated metabolism and calcium signaling
| العنوان: | Dietary cholesterol promotes steatohepatitis related hepatocellular carcinoma through dysregulated metabolism and calcium signaling |
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| المؤلفون: | Lixia Xu, Jun Yu, Narcissus Teoh, Matthew M. Yeh, Sharon Pok, Geoffrey C. Farrell, Eagle S. H. Chu, Ling Dong, Evi Arfianti, W. Geoffrey Haigh, George N. Ioannou, Xiangchun Li, Joseph J.Y. Sung, Jessie Qiaoyi Liang, Jonathan Chiu |
| المصدر: | Nature Communications, Vol 9, Iss 1, Pp 1-13 (2018) Nature Communications |
| بيانات النشر: | Nature Portfolio, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Carcinoma, Hepatocellular, Science, General Physics and Astronomy, Gene Expression, Biology, medicine.disease_cause, Diet, High-Fat, Models, Biological, digestive system, General Biochemistry, Genetics and Molecular Biology, Article, Cholesterol, Dietary, 03 medical and health sciences, Mice, Non-alcoholic Fatty Liver Disease, Gene expression, medicine, Animals, Humans, Calcium Signaling, lcsh:Science, Gene, neoplasms, PI3K/AKT/mTOR pathway, Inflammation, Mutation, Multidisciplinary, Gene Expression Profiling, Liver Neoplasms, nutritional and metabolic diseases, General Chemistry, medicine.disease, digestive system diseases, 3. Good health, Gene expression profiling, Mice, Inbred C57BL, 030104 developmental biology, Cholesterol, Liver, Hepatocellular carcinoma, Cancer research, lcsh:Q, Steatohepatitis, Signal transduction, Metabolic Networks and Pathways |
| الوصف: | The underlining mechanisms of dietary cholesterol and nonalcoholic steatohepatitis (NASH) in contributing to hepatocellular carcinoma (HCC) remain undefined. Here we demonstrated that high-fat-non-cholesterol-fed mice developed simple steatosis, whilst high-fat-high-cholesterol-fed mice developed NASH. Moreover, dietary cholesterol induced larger and more numerous NASH-HCCs than non-cholesterol-induced steatosis-HCCs in diethylnitrosamine-treated mice. NASH-HCCs displayed significantly more aberrant gene expression-enriched signaling pathways and more non-synonymous somatic mutations than steatosis-HCCs (335 ± 84/sample vs 43 ± 13/sample). Integrated genetic and expressional alterations in NASH-HCCs affected distinct genes pertinent to five pathways: calcium, insulin, cell adhesion, axon guidance and metabolism. Some of the novel aberrant gene expression, mutations and core oncogenic pathways identified in cholesterol-associated NASH-HCCs in mice were confirmed in human NASH-HCCs, which included metabolism-related genes (ALDH18A1, CAD, CHKA, POLD4, PSPH and SQLE) and recurrently mutated genes (RYR1, MTOR, SDK1, CACNA1H and RYR2). These findings add insights into the link of cholesterol to NASH and NASH-HCC and provide potential therapeutic targets. Nonalcoholic steatohepatitis (NASH) and dietary cholesterol are risk factors for hepatocellular carcinoma (HCC). Here, the authors utilise mouse models to show that dietary cholesterol induces NASH by deregulating genes involved in metabolism, inflammation and calcium signaling to induce NASH-HCC. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::670ac56f1125499c05760fd30f2fa770 https://doaj.org/article/f586a8b5cf4f4dbbb56141228ef1c3be |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....670ac56f1125499c05760fd30f2fa770 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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