Micro-RNA Prevents Liver Cancer in Mouse Model

They examined the activity of this protein in a mouse model in which some animals were exposed to a carcinogenic chemical that causes liver cancer.

The investigators reported in the December 9, 2011, issue of the journal Cell that disruption of HNF4alpha enabled the activation of a molecular pathway comprising micro RNAs (miRNAs), interleukins, and signaling proteins. The specific molecules involved were miR-124, IL6R, STAT3, miR-24, and miR-629. Once established, this pathway became a self-sustaining inflammatory feedback loop that maintained suppression of HNF4alpha and encouraged oncogenesis.

To break the feedback loop the investigators systematically treated the animals with miR-124. This microRNA modulated inflammatory signaling with the result that is prevented, and suppressed hepatocellular carcinogenesis by inducing tumor-specific apoptosis. Treatment with miR-124 caused no toxic effects in other essential organs, such as the kidneys, spleen, heart, and lungs.

“In this study we are describing for the first time a micro-RNA that is able to prevent and treat liver cancer,” said senior author Dr. Dimitrios Iliopoulos, professor of cancer immunology at the Dana-Farber Cancer Institute. “When HNF4alpha is suppressed, it creates a temporary state of inflammation in the cell – a forerunner of cancer. After only a few days, this transient inflammatory response is converted into a chronic inflammatory response by this feedback circuit that is continuously amplified.”

“We found that miR-124 suppressed more than 80% of tumor growth and size by causing the cancer cells to self-destruct,” said Dr. Iliopoulos. “Our hope is that miR-124 potentially could be used as a preventive in patients at high risk of liver cancer because they have chronic hepatitis C or as a therapeutic agent in patients with liver cancer.”

Related Links:
Dana-Farber Cancer Institute