MicroRNAs in biliary diseases

Abstract

Cholangiopathies are a group of diseases primarily or secondarily affecting bile duct cells, and result in cholangiocyte proliferation, regression, and/or transformation. Their etiopathogenesis may be associated with a broad variety of causes of different nature, which includes genetic, neoplastic, immune-associated, infectious, vascular, and drug-induced alterations, or being idiopathic. miRNAs, small non-coding endogenous RNAs that post-transcriptionally regulate gene expression, have been associated with pathophysiological processes in different organs and cell types, and are postulated as potential targets for diagnosis and therapy. In the current manuscript, knowledge regarding the role of miRNAs in the development and/or progression of cholangiopathies has been reviewed and the most relevant findings in this promising field of hepatology have been highlighted.

Keywords: Cholangiocarcinoma; Cholangiopathies; Polycystic liver diseases; Primary biliary cirrhosis; miRNAs.

Figure 1

miRNA-15a/Cdc25a interplay participates in hepatic cystogenesis of polycystic liver diseases. miRNA-15a directly targets the cell cycle regulator Cdc25a. In polycystic rat and human cholangiocytes, miR15a is downregulated, thus resulting in Cdc25a upregulation, cell proliferation and cystogenesis. The Cdc25a inhibitor vitamin K3 was demonstrated to target Cdc25a, blocking the hepatorenal cystogenesis of several rodent models of polycystic kidney and liver disease. This suggests the therapeutic potential of vitamin K3 for polycystic kidney and liver diseases.

Figure 2

Role of miRNA-506 in the etiopathogenesis of primary biliary cirrhosis. Different risk factors could induce genetic alterations leading to anion exchange 2 (AE2) downregulation in primary biliary cirrhosis (PBC) cholangiocytes. miRNA-506 is overexpressed in PBC cholangiocytes, thus resulting in the inhibition of both AE2 protein translation and subsequent Cl^-/HCO₃^- activity, and impairing the biliary secretory functions.