MicroRNA Replacement Therapy Inhibits Growth of Liver Cancer

An advanced gene therapy technique using adeno-associated virus to implant a specific microRNA (miRNA) suppressed the growth of tumor cells in a mouse model of human liver cancer.

Liver cancer cells have reduced expression of miR-26a, a miRNA that is normally expressed at high levels in diverse tissues. Previous studies have shown that expression of this miRNA in liver cancer cells in vitro induced cell-cycle arrest associated with direct targeting of cyclins D2 and E2.

In the current work, investigators from Johns Hopkins University (Baltimore, MD, USA) worked with a mouse model that closely resembled human liver cancer. To treat the disease they injected adeno-associated virus carrying the gene for a green fluorescent version of miR-26a. A control group received the virus but not the microRNA gene.

Results published in the June 12, 2009, issue of the journal Cell revealed that eight of 10 of animals treated with the miRNA gene were protected from tumor development, exhibiting only small tumors or a complete absence of tumors. In the control group, six of eight mice experienced aggressive disease progression with the majority of their livers replaced by cancerous tissue. There were no indications that the viral therapy had any toxic effects on normal tissues.

"The tumor cells that received the microRNA were rapidly dying while the normal liver cells were completely spared,” said senior author Dr. Josh Mendell, associate professor of genetic medicine at Johns Hopkins University. "These findings, as well as the results of specific tests for liver damage, demonstrated that the microRNA selectively kills the cancer cells without causing any detectable toxic effects on the normal liver or other tissues. This concept of replacing microRNAs that are expressed in high levels in normal tissues but lost in diseases has not been explored before. Our work raises the possibility of a more general therapeutic approach that is based on restoring microRNAs to diseased tissues.”

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