Dietary cholesterol promotes steatohepatitis related hepatocellular carcinoma through dysregulated metabolism and calcium signaling
Liang JQ, Teoh N, Xu L, Pok S, Li X, Chu ESH, Chiu J, Dong L, Arfianti E, Haigh WG, Yeh MM, Ioannou GN, Sung JJY, Farrell G, Yu J
Nature communications · 179 citations
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Independent funding
- University or hospital
- Chinese University of Hong Kong
- University or hospital
- Shenzhen Virtual University Park
- University or hospital
- Shenzhen Research Institute, City University of Hong Kong
- Government
- Medical Research Council
- Government
- National Health and Medical Research Council
- Grants
- National Health and Medical Research Council (1044288); National Health and Medical Research Council (1084136); National Health and Medical Research Council (1120898); National Health and Medical Research Council (585411)
Based on 5 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2018-10-22 · Nat Commun · vol. 9 · issue 1 · p. 4490
- Publisher
- Nature Portfolio
- Cited
- 230 citations · more than 99% of similar papers · 12.9× the field average
- Impact
- Top 10% most cited in its field
- References
- 65 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Liver Disease Diagnosis and Treatment · Cancer, Lipids, and Metabolism · Endoplasmic Reticulum Stress and Disease
- Keywords
- HCCS, Steatohepatitis, Biology, Hepatocellular carcinoma, Steatosis, Cancer research, Cholesterol, Fatty liver, Endocrinology, Internal medicine, Medicine
- MeSH
- liver, animals, mice, inbred c57bl, humans, mice, carcinoma, hepatocellular, liver neoplasms, inflammation, cholesterol, cholesterol, dietary, gene expression profiling, calcium signaling, gene expression, mutation, models, biological, male, metabolic networks and pathways, diet, high-fat, non-alcoholic fatty liver disease
15 authors
From HK, CN, AU, US
- Qiaoyi LiangChinese University of Hong Kong; Chinese University of Hong Kong, Shenzhen
- Narcissus TeohAustralian National University; Canberra Hospital
- Lixia XuChinese University of Hong Kong; Chinese University of Hong Kong, Shenzhen
- Sharon PokAustralian National University; Canberra Hospital
- Xiangchun LiChinese University of Hong Kong; Chinese University of Hong Kong, Shenzhen
- Eagle S.H. ChuChinese University of Hong Kong; Chinese University of Hong Kong, Shenzhen
Abstract
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
Community trust
Loading…
How much do you trust this study's findings?
Comments
Sign in to rate, comment on or flag this study.Sign inSomething wrong here?
Flag this study if its information, labels or funding look wrong. An editor reviews every flag.
Sign in to rate, comment on or flag this study.Sign inEducational information about published research. Not medical advice, and not a recommendation to start or stop anything.