Nonalcoholic steatohepatitis (NASH) is part of a spectrum of nonalcoholic fatty liver disease (NAFLD) and can progress to cirrhosis in 15% of subjects.1 The mechanisms by which NASH develops and progresses to cirrhosis have not been fully defined.
MicroRNAs (miRNA) are non–protein-coding, small single-stranded RNA, typically 21 to 23 nucleotides long, that regulate gene expression via messenger RNA (mRNA) degradation or translational inhibition.2, 3 Currently, 873 human miRNAs have been identified (miRBase 11.0, April 2008). Their expression is both organ-specific and dependent on the stage of development.4, 5 Micro RNAs also regulate other important cellular processes such as metabolism, immune function, cell proliferation, apoptosis, and tissue development and differentiation.6–10 These may be particularly germane to the genesis of NASH, which is characterized by abnormal lipid metabolism, activation of apoptosis, cellular regenerative responses, and inflammation.11 There are currently no published data on the patterns of hepatic miRNA expression in NASH.
The aims of this study were to: (1) identify differentially expressed miRNAs in human NASH and validate these independently; (2) tabulate potential targets of differentially expressed miRNAs; and (3) evaluate and compare the effects of silencing and overexpression of a specific differentially expressed miRNA, microRNA (miR-122), which is known to target hepatic lipogenic genes, on the pattern of lipogenic gene expression in human NASH. It is hoped that these data would serve as the basis for future hypothesis generation and hypothesis-driven studies of the role of miRNAs in hepatic lipid metabolism and pathogenesis of NASH.