MicroRNAs in the Cholangiopathies: Pathogenesis, Diagnosis, and Treatment

Abstract

The cholangiopathies are a group of liver diseases resulting from different etiologies but with the cholangiocyte as the primary target. As a group, the cholangiopathies result in significant morbidity and mortality and represent one of the main indications for liver transplant in both children and adults. Contributing to this situation is the absence of a thorough understanding of their pathogenesis and a lack of adequate diagnostic and prognostic biomarkers. MicroRNAs are small non-coding RNAs that modify gene expression post-transcriptionally. They have been implicated in the pathogenesis of many diseases, including the cholangiopathies. Thus, in this review we provide an overview of the literature on miRNAs in the cholangiopathies and discuss future research directions.

N‐myc downstream‐regulated gene 2 inhibits human cholangiocarcinoma progression and is regulated by leukemia inhibitory factor/MicroRNA‐181c negative feedback pathway

“…NDRG2 also inhibits metastasis of CCA cells, as determined by in vitro transwell, wound healing, and in vivo liver, lung, and intraperitoneal metastatic assays. Most important, our results show that lower NDRG2 expression is associated with poorer OS of CCA patients, indicating that NDRG2 could be an important prognostic marker for CCA patients.miRNA deregulation is frequently observed in human cancers, including CCA . In this study, we explored the possibility of miRNA deregulation is a contributing factor in NDRG2 low expression in CCA.…”

Effects of miR-27a upregulation on thyroid cancer cells migration, invasion, and angiogenesis

“…The regulatory role of miRNAs in protein synthesis under physiological conditions is extremely important. miRNA dysregulation is associated with a variety of human cancers, including thymic carcinoma (Joyce et al, 2016), liver cancer (Otsuka et al, 2016), and bile duct carcinoma (Pisarello et al, 2015;Mutalib et al, 2016). Different miRNAs play critical roles in different kinds of malignant tumors.…”

Diagnostic and therapeutic potentials of microRNAs in cholangiopathies

“…These three PLD-causing diseases arise from different inherited genetic mutations; development of ADPLD is due to mutations in protein kinase C substrate 80K-H ( PRKCSH ) and/or translocation protein SEC63 homolog ( SEC63 ) genes; ADPKD is caused by mutations in the polycystin-1 and -2 ( PKD-1 and PKD-2 ) genes; and ARPKD is due to mutations in the polycystic kidney and hepatic disease-1 ( PKHD-1 ) gene [74]. Further perturbation of PLD occurs by malformation of the ductal plate and abnormal cell signaling and function [23]. Currently, therapeutic intervention relies heavily on the use of somatostatin analogs, and while these treatments tend to significantly decrease liver volume, there is only a slight improvement in symptoms [75].…”

“…As previously stated, cholangiocytes begin to proliferate and secrete neuroendocrine factors in response to damage, and this cellular function has been largely characterized during the progression of cholangiopathies [1, 8, 10]. Recently, however, microRNAs (miRNAs) have been recognized as initiators and/or drivers of some cholangiopathies [21-23]. …”