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Emerging role of miR-21 in non-alcoholic fatty liver disease
  1. Samira Benhamouche-Trouillet1,
  2. Catherine Postic2,3,4
  1. 1 BordeAux Research in Translational Oncology, Univ. Bordeaux, INSERM, U1053, Bordeaux, France
  2. 2 Inserm, U1016, Institut Cochin, Paris, France
  3. 3 CNRS UMR 8104, Paris, France
  4. 4 Université Paris Descartes, Sorbonne Paris Cité, Paris, France
  1. Correspondence to Dr Samira Benhamouche, Univ. Bordeaux, INSERM, U1053, BordeAux Research in Translational Oncology, BaRITOn, Bordeaux F-33076, France; samira.benhamouche{at}inserm.fr

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Non-alcoholic fatty liver disease (NAFLD) has recently been linked to hepatocellular carcinoma (HCC) development, with or without the presence of cirrhosis, both in human disease and animal models. NAFLD is the hepatic manifestation of the metabolic syndrome associated with obesity, hyperinsulinaemia, type 2 diabetes, insulin resistance, hypertriglyceridaemia and hypertension, affecting up to one-third of the population worldwide.1 The diagnosis is related to the presence of excess liver droplets accumulation that can progress from hepatic steatosis to inflammation-associated steatohepatitis (non-alcoholic steatohepatitis, NASH). The pathogenesis of NAFLD is a highly integrated process, and a so-called ‘two-hit’ model is prevailing: the first hit is insulin resistance leading to fat accumulation through unabated lipolysis from the adipose tissue and increased de novo lipogenesis from glucose in the hepatocytes; hepatocyte fat accumulation will lead to the second hit associated with oxidative stress, cellular injury, inflammation and fibrosis. Many factors such as release of free fatty acids from adipose tissue, reactive oxidative stress species, interleukin-6, tumour necrosis factor-α and alteration in key signalling pathways (inflammation, insulin) are proposed to be involved in the pathological processes of NAFLD.

Interestingly, recent evidence indicates that changes in microRNAs (miRNAs) expression may be associated with NAFLD, NASH and related cardiovascular diseases.2 miRNAs are highly conserved 18–25 nucleotide non-coding RNA that regulate gene expression at the post-transcriptional level by destabilising mRNA and/or inhibiting translation. By regulating various target genes, miRNAs play pivotal roles in fine-tuning of metabolic processes in hepatocytes. Their stability in blood circulation makes them attractive biomarkers and potential therapeutic targets for liver …

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