CHICAGO, Jan. 22 (Xinhua) -- A study at Washington University School of Medicine in St. Louis indicates that an RNA binding protein involved in regulating lipid levels in the liver and blood promotes development and progression of fatty liver disease and liver cancer in mice.
The researchers studied how certain RNA binding proteins, proteins that play a role in various cellular processes such as function and transport, regulate the RNA building blocks that contribute to the synthesis of proteins involved in liver cancer and other gastrointestinal diseases.
They studied the genetic regulation of metabolism in the intestine and the liver, with a particular focus on obesity and fatty liver, and have focused on how a particular RNA binding protein called Apobec1 complementation factor (A1CF) operates in the liver.
In the experiments, the researchers engineered mice that make extra amounts of the protein in hepatocytes, which make up about 80 percent of the cells in the liver. The mice produced about two to three times the normal amount of the protein.
The researchers found that mice with excessive amounts of the protein developed fatty liver disease even when eating a low-fat diet, and as the mice aged, most developed liver cancer.
After noticing that mice with extra amounts of the protein developed fatty liver disease and liver cancer, the researchers examined tissue samples from patients who had liver cancer and found that these tissue samples also contained elevated levels of the protein.
"We found that as these transgenic mice aged, they developed fatty liver spontaneously, regardless of their diet, though the condition was worse in mice that ate a high-fat, high-fructose diet," said senior investigator Nicholas O. Davidson, director of the university's Division of Gastroenterology. "As the animals got even older, the mice developed scarring and fibrosis of the liver, and eventually, most developed liver cancer. When we looked at liver cancer tissue from humans with fatty liver disease, we found extra amounts of the same RNA binding protein there, too."
The findings suggest that in addition to being involved in the regulation of lipids, the protein also plays a role in the development of liver cancer.
"Liver cancer has been difficult to study because of regional differences throughout the liver, and there isn't a dominant set of tumor drivers such as with other types of cancer, like breast or colon cancer," Davidson said. "A better understanding of how the over-expression of this RNA binding protein promotes liver cancer could be important to learning how fatty liver disease contributes to cancer risk and perhaps to predict which tumors in the liver might be more aggressive."
Nonalcoholic fatty liver disease is believed to affect as many as a billion people in the world, some 80 million to 100 million of them in the United States. Meanwhile, about 40,000 individuals are diagnosed with liver cancer each year in the United States, a number that has tripled during the last two decades.
The findings, posted on the university's website on Wednesday, have been published online in The Journal of Clinical Investigation. Enditem
