Novel therapeutic approach to combat liver cancer identified

They demonstrated in a mouse model that a particular micro-RNA (miR-124) – a member of a recently discovered class of molecular regulators – could be harnessed to treat or even prevent the dreaded disease.

“In this study we are describing for the first time a micro-RNA that is able to prevent and treat liver cancer,” Dimitrios Iliopoulos,of Dana-Farber’s Department of Cancer Immunology and AIDS said.

Iliopoulos and his colleagues found that in mice given a carcinogenic chemical,DEN,liver cancer was initiated by the activation of a molecular circuit that sets up an inflammatory state in the cells,leading to cancer.

Once this inflammatory circuit is turned on even for a few days,it becomes permanent,sustaining its activity through a never-ending feedback loop – a “snowball effect,” as Iliopoulos termed it.

According to the Dana-Farber team,one element of the circuit is a micro-RNA called miR-124.

The research team found that miR-124 and another key controller of the feedback circuit,HNF4a,showed reduced activity in the cancer cells.

Because HNF4a and miR-124 interact with each other,the scientists hypothesized that boosting activity of miR-124 might restore normal activity in HNF4a,halting the runaway inflammatory cycle and causing tumors to stop growing.

To test this notion they administered systemically miR-124 once a week for four weeks to mice that had developed liver cancer by exposure to DEN.

“We found that miR-124 suppressed more than 80 per cent of tumor growth and size by causing the cancer cells to self-destruct,” the scientists wrote.

They further showed that giving miR-124 to mice exposed to DEN actually prevented the development of liver tumors.

The findings are being published on Dec 9 in the journal Cell.