MicroRNA miR-122 as a therapeutic target for oligonucleotides and small molecules.

The most abundant microRNA (miRNA) in the liver, miR-122, is regulated by specific, liver-enriched transcription factors and is responsible for proper proliferation and differentiation of hepatocytes and for the regulation of lipid and cholesterol metabolisms. miR-122 is also involved in several hepatic disorders, as downregulation of miR-122 is often associated with hepatocellular carcinoma (HCC) and miR-122 is a required component for the replication and proliferation of the hepatitis C virus (HCV). Various probes have been developed to promote a better understanding of the involvement of miR-122 in liver diseases, including modified antisense agents and small molecule inhibitors. These agents, capable of specifically modifying miR-122 activity, provide excellent tools to investigate the function and regulation of miR-122 and offer potential new lead compounds for drug discovery. Especially small molecule modifiers can display numerous advantages over nucleotide analogs, as discussed in this review.