Role of Circulating microRNAs in Liver Disease and HCC: Focus on miR-122

Abstract

miR-122 is the most abundant microRNA (miRNA) in the liver; it regulates several genes mainly involved in cell metabolism and inflammation. Host factors, diet, metabolic disorders and viral infection promote the development of liver diseases, including hepatocellular carcinoma (HCC). The downregulation of miR-122 in tissue is a common feature of the progression of liver injury. In addition, the release of miR-122 in the bloodstream seems to be very promising for the early diagnosis of both viral and non-viral liver disease. Although controversial data are available on the role of circulating miR-122 as a single biomarker, high diagnostic accuracy has been observed using miR-122 in combination with other circulating miRNAs and/or proteins. This review is focused on comprehensively summarizing the most recent literature on the potential role of circulating miR-122, and related molecules, as biomarker(s) of metabolic liver diseases, hepatitis and HCC.

Keywords: HBV; HCC; HCV; NAFLD; diagnostic biomarkers; liver disease; miR-122; miRNAs.

Figure 1

Representation of miR-122 biogenesis and function in the liver. (A) Mature miR-122 modulates hepatocyte differentiation, inflammation. Amino acid and ion transport, cell proliferation and migration, and promotes lipogenesis. (B) Picture obtained from miRNET database (https://www.mirnet.ca/, accessed on 8 September 2024) showing the main experimentally validated target genes of miR-122. In particular, miR-122 regulates cell proliferation and migration by interacting with LMNB2, ADAM10, ADAM17, CCNG1, SRF and IGF1R mRNA. MiR-122 regulates metabolism and ion/amino acid transport by interacting with ALDOA and SLC7A1 mRNA. (C) During HCV infection in hepatocytes, mature miR-122 stabilizes HCV genome by interacting with IRES at 5′-end and promotes viral genome translation.