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 citas
Cómo se estudió
- Diseño
- Estudio en animales (clasificado por nuestro filtro de IA)
- Estudiado en
- Personas, más trabajo en animales o laboratorio
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiación independiente
- Universidad u hospital
- Chinese University of Hong Kong
- Universidad u hospital
- Shenzhen Virtual University Park
- Universidad u hospital
- Shenzhen Research Institute, City University of Hong Kong
- Gobierno
- Medical Research Council
- Gobierno
- National Health and Medical Research Council
- Subvenciones
- 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)
Según 5 financiadores declarados y la declaración de financiación del texto completo.
Publicación
- Publicado
- 2018-10-22 · Nat Commun · vol. 9 · número 1 · pág. 4490
- Editorial
- Nature Portfolio
- Citado
- 222 citas · más que el 99% de estudios similares · 5.6× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 65 trabajos
- Acceso
- Acceso abierto (revista) · CC-BY
- Áreas de investigación
- Liver Disease Diagnosis and Treatment · Cancer, Lipids, and Metabolism · Endoplasmic Reticulum Stress and Disease
- Palabras clave
- 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 autores
- Qiaoyi Liang🇭🇰🇨🇳Chinese University of Hong Kong; Chinese University of Hong Kong, Shenzhen
- Narcissus Teoh🇦🇺Australian National University; Canberra Hospital
- Lixia Xu🇭🇰🇨🇳Chinese University of Hong Kong; Chinese University of Hong Kong, Shenzhen
- Sharon Pok🇦🇺Australian National University; Canberra Hospital
- Xiangchun Li🇭🇰🇨🇳Chinese University of Hong Kong; Chinese University of Hong Kong, Shenzhen
- Eagle S.H. Chu🇭🇰🇨🇳Chinese University of Hong Kong; Chinese University of Hong Kong, Shenzhen
- Jonathan B. Chiu🇭🇰🇨🇳Chinese University of Hong Kong; Chinese University of Hong Kong, Shenzhen
- Ling Dong🇨🇳Sun Yat-sen University; Fudan University; Zhongshan Hospital; The First Affiliated Hospital, Sun Yat-sen University
- Arfianti Arfianti🇦🇺Australian National University; Canberra Hospital
- W. Geoffrey Haigh🇺🇸University of Washington; VA Puget Sound Health Care System
- Matthew M. Yeh🇺🇸University of Washington
- George N. Ioannou🇺🇸University of Washington; VA Puget Sound Health Care System
- Joseph J.�Y. Sung🇭🇰🇨🇳Chinese University of Hong Kong; Chinese University of Hong Kong, Shenzhen
- Geoffrey C. Farrell🇦🇺 · autor de correspondenciaAustralian National University; Canberra Hospital
- Jun Yu🇭🇰🇨🇳 · autor de correspondenciaChinese University of Hong Kong; Chinese University of Hong Kong, Shenzhen
Resumen
El texto original del estudio, en el idioma en que se publicó.
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.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY).
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