NONALCOHOLIC STEATOHEPATITIS IS ASSOCIATED WITH ALTERED HEPATIC MICRO RNA EXPRESSION

By Onpan Cheung, P. Puri, C. Eicken, M. Contos, F. Mirshahi, J. Maher, J. Kellum, H. Min, V. Luketic, Arun J Sanyal. Hepatology, 2008

676 citations recorded by the source corpus.

The expression of microRNA in nonalcoholic steatohepatitis (NASH) and their role in the genesis of NASH are not known. The aims of this study were to: (1) identify differentially expressed microRNAs in human NASH, (2) tabulate their potential targets, and (3) define the effect of a specific differentially expressed microRNA, miR‐122, on its targets and compare these effects with the pattern of expression of these targets in human NASH. The expression of 474 human microRNAs was compared in subjects with the metabolic syndrome and NASH versus controls with normal liver histology. Differentially expressed microRNAs were identified by the μParaflo microRNA microarray assay and validated using quantitative real‐time polymerase chain reaction (PCR). The effects of a specific differentially expressed miRNA (miR‐122) on its predicted targets were assessed by silencing and overexpressing miR‐122 in vitro. A total of 23 microRNAs were underexpressed or overexpressed. The predicted targets of these microRNAs are known to affect cell proliferation, protein translation, apoptosis, inflammation, oxidative stress, and metabolism. The miR‐122 level was significantly decreased in subjects with NASH (63% by real‐time PCR, P < 0.00001). Silencing miR‐122 led to an initial increase in mRNA levels of these targets (P < 0.05 for all) followed by a decrease by 48 hours. This was accompanied by an increase in protein levels of these targets (P < 0.05 for all). Overexpression of miR‐122 led to a significant decrease in protein levels of these targets. Conclusions: NASH is associated with altered hepatic microRNA expression. Underexpression of miR‐122 potentially contributes to altered lipid metabolism implicated in the pathogenesis of NASH. (HEPATOLOGY 2008;48:1810–1820.)

Subfields: Cancer Research, Epidemiology, Hepatology

View Paper: https://www.semanticscholar.org/paper/878014943c0453f6e3ffab6b1fb22192faed9118

How researchers see this paper

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In Cancer Research

1. Gerald I. Shulman
2. Yu Li
3. S. Pfeffer
4. Kris V. Kowdley
5. S. Friedman

In Epidemiology

1. S. Friedman
2. M. Pinzani
3. T. Baumert
4. R. Loomba
5. Gerald I. Shulman
6. A. Sanyal
7. E. Tsochatzis
8. E. Buzzetti

In Hepatology

1. S. Friedman
2. M. Pinzani
3. T. Baumert
4. R. Loomba
5. Gerald I. Shulman
6. A. Sanyal
7. Ralf Weiskirchen
8. Y. Saiman

Citations in the corpus

• Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver. (2012, neutral): “…underlying liver dysfunction, especially chronic inflammation and cirrhosis. miR-122 expression is reduced during the initiation and progression of hepatocarcinogenesis in a rat model of nonalcoholic steatohepatitis (NASH) (8), and downregulation of miR-122 is prevalent in human NASH patients (9).”
• Mechanisms and disease consequences of nonalcoholic fatty liver disease (2021, background): “Additional miRNAs implicated in NAFLD include miR-122 (Cheung et al., 2008), miR-21 (Benhamouche-Trouillet and Postic, 2016), miR-124a (Fang et al.”
• miR-122--a key factor and therapeutic target in liver disease. (2015, background): “Although this knowledge has been acquired using mouse models, it is important to note that reduced miR122 expression has been associated with human non-alcoholic steatohepatitis [42] extending the relevance of these findings to”
• INCREASED HEPATIC SYNTHESIS AND DYSREGULATION OF CHOLESTEROL METABOLISM IS ASSOCIATED WITH THE SEVERITY OF NONALCOHOLIC FATTY LIVER DISEASE (2012, methodology): “MiR-34a is a microRNA that is overexpressed in NASH (Cheung et al., 2008).”
• MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis. (2012, neutral): “More-over, pathogenic repression of miR-122 has been observed in non-alcoholic steatohepatitis (11), liver cirrhosis (12), and hepatocellular carcinoma (HCC) (12–16).”
• Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties (2009, neutral): “E-mail: snorri_s_thorgeirsson@nih.gov Oncogene (2009) 28, 3526–3536 & 2009 Macmillan Publishers Limited All rights reserved 0950-9232/09 $32.00 www.nature.com/onc 2008; Lin et al., 2008) as well as in nonalcoholic steatohepatitis (Cheung et al., 2008).”
• MicroRNAs in Common Human Diseases (2012, background): “Furthermore, abnormal expression of miR-29c, miR-34a, miR-155, and miR-200b were found in a mouse model of non-alcoholic steatohepatitis (NASH) [88], in addition to 23 more identified in tissues from NASH patients by miRNA microarrays [89].”
• The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). (2016, background): “Variations in the expression and circulating levels of miRNAs have been linked to the pathogenesis of NAFLD/ NASH: several miRNAs are differentially expressed in subjects withNASHand are associatedwith glucose and lipidmetabolism [113,114].”