A microRNA With Macro Implications
miR-122 expression might predict survival of liver-cancer patients
A molecule called microRNA-122 (miR-122) is critical for regulating liver-cell metabolism and for suppressing liver-cancer development. A study led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) and at Rockefeller University’s Howard Hughes Medical Institute shows that miR-122 interacts with thousands of genes in liver cells. Levels of this molecule often drop during liver-cancer development, and the study also found that when this happens, the expression of certain cancer-promoting genes goes up.
The findings could one day help doctors better predict survival in liver cancer patients and help determine whether miR-122 should be developed as an anticancer drug.
The researchers sought to biochemically (rather than computationally) define all miR-122 target sites in the liver and hepatocellular carcinoma (HCC), the most common form of liver cancer, and to learn which target genes were critical for liver-cancer development or progression. miR-122 is found almost exclusively in liver cells, where its role includes regulating cholesterol and lipid metabolism.
“We want to understand how miR-122 regulates liver metabolism and suppresses cancer development, and to identify common targets in humans and mice that may be involved in HCC development,” says co-principal investigator and OSUCCC – James researcher Kalpana Ghoshal, PhD, associate professor of pathology. “That knowledge is critical for determining whether this molecule should be developed as a possible therapeutic agent for liver cancer.”
Ghoshal and her colleagues conducted their study using a mouse model that lacked miR-122, along with normal mice; liver cancer tissues and normal liver tissues from nine HCC patients; and data from 373 HCC patients in The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset.
The findings significantly extend the number of miR-122 binding sites identified by earlier studies because the methods used by the investigators identified sites that other techniques miss, Ghoshal adds. (Note: One gene can have multiple microRNA target sites.)
Published in the journal Molecular Cell.