Primary biliary cirrhosis is associated with altered hepatic microRNA expression

Abstract

MicroRNAs (miRNAs) are small RNA molecules that negatively regulate protein coding gene expression and are thought to play a critical role in many biological processes. Aberrant levels of miRNAs have been associated with numerous diseases and cancers, and as such, miRNAs have gain much interests as diagnostic biomarkers, and as therapeutic targets. However, their role in autoimmunity is largely unknown. The aims of this study are to: (1) identify differentially expressed miRNAs in human primary biliary cirrhosis (PBC); (2) validate these independently; and (3) indentify potential targets of differentially expressed miRNAs. We compared the expression of 377 miRNAs in explanted livers form subjects with PBC versus controls with normal liver histology. A total of 35 independent miRNAs were found to be differentially expressed in PBC (p< 0.001). Quantitative PCR was employed to validate down-regulation of microRNA-122a (miR-122a) and miR-26a and the increased expression of miR-328 and miR-299-5p. The predicted targets of these miRNAs are known to affect cell proliferation, apoptosis, inflammation, oxidative stress, and metabolism. Our data are the first to demonstrate that PBC is characterized by altered expression of hepatic miRNA; however additional studies are required to demonstrate a causal link between those miRNA and the development of PBC.

The role of miR-26 in tumors and normal tissues (Review)

“…Padgett et al observed that a total of 35 independent miRNAs in the miRNA expression profile are disordered and that miR-26a is one of the down-regulated miRNAs. The predicted targets of these alternative miRNAs are known to affect cell proliferation, apoptosis, inflammation, oxidative stress and metabolism associated with the development of PBC (31). The roles that miR-26 plays in non-tumor diseases have yet to be clarified, and further studies are required.…”

The liver-specific microRNA miR-122 controls systemic iron homeostasis in mice

“…24). miR-122 is an abundant, liver-specific miRNA (25,26) whose expression is decreased in advanced liver diseases, such as cirrhosis (27) and hepatocellular carcinoma (28,29). Several independent studies demonstrate that in vivo inhibition of miR-122 reduces systemic cholesterol levels by as-yet unidentified molecular mechanisms (30,31).…”

The Crosstalk between Micro RNA and Iron Homeostasis

“…The finding that miR-122 regulates systemic iron homeostasis adds to a growing list of liver functions that are controlled by miR-122. For example, miR-122 levels are decreased in advanced liver diseases such as cirrhosis and hepatocellular carcinoma pathologies known to be exacerbated by increased liver iron levels [95][96][97][98].…”