Reversing Loss of miR-122 Helps Treat Liver Cancer

The animal study was led by researchers at the Ohio State University (OSU) Comprehensive Cancer Center-Arthur G. James Cancer Hospital (Columbus, USA) and OSU’s Richard J. Solove Research Institute (OSUCCC-James). The scientists examined what occurs when liver cells lack a molecule called microRNA-122 (miR-122). They found that when the molecule is missing, the liver develops fat deposits, inflammation, and tumors that resemble hepatocellular carcinoma (HCC), the most common form of liver cancer.

When the researchers synthetically restored miR-122 to nearly normal levels by delivering the miR-122 gene into liver cells, it considerably reduced the size and number of tumors, with tumors making up 8% on average of liver surface area in treated animals versus 40% in control animals.

The study was published July 23, 2012, in the Journal of Clinical Investigation. “These findings reveal that miR-122 has a critical tumor-suppressor role in the healthy liver, and they highlight the possible therapeutic value of miR-122 replacement for some patients with liver cancer,” said study leader Dr. Kalpana Ghoshal, associate professor of pathology and a member of the OSUCCC-James Experimental Therapeutics Program.

MiR-122 is found principally in liver cells--it is the most plentiful microRNA in those cells--and it plays a major role in regulating cholesterol in the body. This microRNA is lost in some people with HCC, however, resulting in a poor prognosis.

For this study, Dr. Ghoshal and her colleagues developed a strain of mice that lacks miR-122 and develops HCC through the progression of events that begins with fatty liver deposits followed by inflammation and liver cancer. The researchers then used a second strain of mice that spontaneously develops liver cancer due to overexpression of a cancer-causing gene called MYC. The researchers delivered miR-122 into the animals’ livers during tumor development. Three weeks later, those treated with the molecule had smaller and fewer tumors. “The model we developed for these studies will not only facilitate our understanding of liver biology, but it will also be good for testing therapeutic efficacy of newly developed drugs against liver disease, including HCC,” Dr. Ghoshal stated.

Dr. Ghoshal also noted that research by other scientists has shown that Hepatitis C virus requires miR-122 for replication. “Because our findings demonstrate what happens when miR-122 is lost in liver cells, they might help improve the safety of new drugs that treat Hepatitis C virus infection by blocking miR-122,” she concluded.

Related Links:
Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital