Loss of microRNA might lead to hepatocellular carcinoma
Developing a drug that restores microRNA-122 levels might offer a new way to treat this type of cancer
- Date : 02 Aug 2012
- Topic : Gastrointestinal cancers
A new study shows that loss of microRNA in liver cells might cause hepatocellular carcinoma and that restoring the molecule might slow tumour growth and offer a new way to treat the disease.
This preclinical study was led by researchers at the Ohio State University Comprehensive Cancer Centre – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James). The scientists examined what happens when liver cells lack a microRNA-122 (miR-122). They found that when the molecule is missing, the liver develops fat deposits, inflammation and tumours that resemble hepatocellular carcinoma, the most common form of liver cancer.
When the researchers artificially restored miR-122 to nearly normal levels by delivering the miR-122 gene into liver cells, it dramatically reduced the size and number of tumours, with tumours making up 8% on average of liver surface area in treated animals versus 40% in the control group.
The study was published in the Journal of Clinical Investigation.
The study findings reveal that miR-122 has a critical tumoUr-suppressor role in the healthy liver
The findings from this study highlight the possible therapeutic value of miR-122 replacement for some patients with hepatocellular carcinoma. MiR-122 is found mainly in liver cells – it is the most abundant microRNA in those cells – and it plays a major role in regulating cholesterol in the body. This microRNA is lost in some people with hepatocellular carcinoma, however, resulting in a poor prognosis.
For this study, Dr Kalpana Ghoshal, associate professor of pathology and a member of the OSUCCC – James Experimental Therapeutics Program, who was a study leader with her colleagues developed a strain of mice that lacks miR-122 and develops hepatocellular carcinoma 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 MYC. The researchers delivered miR-122 into the animals' livers during tumour development. Three weeks later, those treated with the molecule had smaller and fewer tumours.
The model they developed for these studies will not only facilitate understanding of liver biology, but it will also be good for testing therapeutic efficacy of newly developed drugs against liver diseases, including hepatocellular carcinoma.
The research by others has shown that hepatitis C virus requires miR-122 for replication. Because findings from this study 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.
The study was funded from the USA NIH/National Cancer Institute (grants CA086978, CA120185 and CA134292), NIH/ National Institute of Diabetes and Digestive and Kidney Diseases (grant DK088076), a Pelotonia idea grant, a Pelotonia predoctoral fellowship, and the Cancer Prevention and Research Institute of Texas supported this research.
Other researchers involved in this study were scientists of The Ohio State University, Nationwide Children's Hospital, Johns Hopkins University School of Medicine, and UT Southwestern Medical Centre.
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