Investigating the link between
noncoding RNAs and alcoholic liver disease

Alcoholic liver disease is a term that describes a wide range of damage caused by the overconsumption of alcohol, including fatty liver, cirrhosis, hepatitis and increased risk of hepatocellular carcinoma. Due to the variety of factors that likely influence alcoholic liver disease (both genetic and environmental), it is difficult to define the precise mechanisms by which alcohol induces liver damage.

Recent studies have implicated microRNAs (called miRNAs for short) in the regulation of hepatic cell proliferation and survival during alcoholic liver injury via their ability to switch off specific target genes. Authors of a recent article in the Journal of Biological Chemistry investigated the precise mechanisms by which miRNAs contribute to cellular responses in alcoholic liver disease.

Heather Francis, Gianfranco Alpini and Fanyin Meng of the Central Texas Veterans Health Care System and collaborators in China began by identifying the miRNAs that were differentially overexpressed in livers from mice that were fed ethanol compared with controls. They found that 0.8 percent of known miRNAs in the mouse liver were upregulated in the ethanol-fed group. Of those, the most upreglated miRNA was miR-21.

Upon in vitro overexpression of miR-21, cell survival was increased in three different cell types from human liver, indicating a possible role for miR-21 in regulating the survival of hepatic cells in alcoholic liver disease. Indeed, the authors found that miR-21, which they determined is regulated by IL-6/Stat3 signaling, regulates cell survival by targeting two well-characterized genes involved in the apoptotic pathway, FASLG and DR5.

Although IL-6/Stat3 signaling has been implicated previously in alcoholic liver disease, this is the first known linkage to alcohol-dependent miRNA expression. The identification of other noncoding RNAs and their targets involved in alcoholic liver disease may provide key insights into the development of improved diagnosis and novel therapeutic approaches for treating patients.

Jen McGlaughon Jen McGlaughon (jla254@cornell.edu) is graduate student in the molecular biology and genetics department at Cornerll University.