MicroRNAs in liver disease

Abstract

Small, noncoding microRNAs (miRNAs) regulate diverse biological functions in the liver and increasing evidence suggests that they have a role in liver pathology. This Review summarizes advances in the field of miRNAs in liver diseases, inflammation and cirrhosis. MicroRNA-122, the most abundant miRNA in hepatocytes, has well-defined roles in HCV replication, and data indicate that it also serves as a viable therapeutic target. The role of miR-122 is also emerging in other liver diseases. Ample evidence exists for the important regulatory potential of other miRNAs in conditions associated with liver inflammation related to alcohol use, the metabolic syndrome or autoimmune processes. In addition, a broad array of miRNAs have been associated with the development of liver fibrosis both in animal models and human studies. The significance of the function and cellular distribution of miRNAs in the liver and the potential of miRNAs as a means of communication between cells and organs is discussed as well as the emerging utility of circulating miRNAs as biomarkers of different forms of liver damage and as early markers of disease and progression in hepatocellular carcinoma. Importantly, miRNA modulation in the liver represents a new therapeutic approach in the treatment armamentarium of hepatologists in the future.

Prospective evidence of a circulating microRNA signature as a non-invasive marker of hepatocellular carcinoma in HBV patients

“…In line with our findings, a recent study [19] showed that 3 serum miRNAs, including let-7f, could separate HBV-HCC cases from controls. MiR-122, the most abundant liver-specific miRNA, is considered a suppressor of cell proliferation and malignant transformation of hepatocytes with remarkable tumor inhibition activity [32][33][34]. Interestingly, although downregulation of miR-122 was frequently reported in the HCC tumor tissues [2,34,35], Qi et al [36] showed that miR-122 in serum was elevated in HCC patients and markedly reduced in post-operative serum samples, which is consistent with the observation in our study.…”

MiR-29a Assists in Preventing the Activation of Human Stellate Cells and Promotes Recovery From Liver Fibrosis in Mice

“…9,10 The sequence between mmu-miR-29a and hsa-miR29a was conserved across species (http://www.mirbase.org). We evaluated the ability of miR-29a to improve liver fibrosis using CCl 4 and TAA models established in Figure 1.…”

“…7 Aberrant expression of miRNA is associated with the progression of liver fibrosis. [8][9][10] For example, the expression of miR-132 and the miR-29 family (miR-29a, miR29b, and miR-29c) is significantly underexpressed in fibrotic livers, as demonstrated in human liver cirrhosis and in liver injury models induced by bile duct ligation and carbon tetrachloride (CCl 4 ) in mice. Downregulation of these miRNAs can modify the activity of HSCs.…”

Clinical Outcomes and Genetic Expression Profile in Human Liver Graft Dysfunction During Ischemia/Reperfusion Injury

“…The data presented herein support these findings, demonstrating the importance of inflammasomes and IL-1b release in the process of IRI. Other known data, such as cold ischemia time, warm ischemia time, and other specific donor conditions, cannot be ignored and are described widely [24,25]. Nonetheless, the different clinical outcomes of IRI and the different clinical presentation, can be, at least partially, attributed to different gene expression of IL-1b in donor livers, leading to a more significant inflammatory process during IRI in OLT [26,27].…”