microRNAs: fad or future of liver disease

Abstract

microRNAs (miRs) are small non-coding RNAs that regulate both mRNA and protein expression of target genes, which results in alterations in mRNA stability or translation inhibition. miRs influence at least one third of all human transcripts and are known regulators of various important cellular growth and differentiation factors. miRs have recently emerged as key regulatory molecules in chronic liver disease. This review details recent contributions to the field of miRs that influence liver development and the broad spectrum of disease, from non-alcoholic fatty liver disease to fibrosis/cirrhosis, with particular emphasis on hepatic stellate cells and potential use of miRs as therapeutic tools.

Keywords: Fibrosis; Hepatic stellate cells; Liver; mRNA; microRNA.

Figure 1

microRNAs involved in hepatic stellate cell transdifferentiation. Functional manipulation studies utilizing mimics and/or antagomirs have demonstrated that the miRs depicted in the above schematic regulate key genes/functions in hepatic stellate cells (HSCs). (Quiescent HSC: yellow circles represent cytoplasmic lipid droplets; activated HSC: purple lines indicate cytoskeletal protein smooth muscle alpha actin; green oval represents Bcl-2; red fibrils represent collagen). Additional profiling studies have shown upregulation of several microRNAs (miRs) in both phenotypes, some of which are already associated with hepatic disease (boxes contain a small fraction of published miRs). References[38-43,47] were used to generate the contents of this figure with design software BioDraw Ultra 12.0.