MicroRNA replacement provides an effective therapy in cancer
Researchers from Johns Hopkins and Nationwide Children have discovered a potential strategy for cancer therapy by focusing on what’s missing in tumors. MicroRNAs control gene expression and are commonly lost in cancerous tumors.
Noticing this absence, scientists have shown that the replacement of a single microRNA in mice with an extremely aggressive form of liver cancer can be enough to halt their disease and have published the results in Cell, June 12.
Josh Mendell, M.D., Ph.D., an associate professor in the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine says “This work suggests that microRNA replacement may be a highly effective and nontoxic treatment strategy for some cancers or even other diseases,” and “We set out to learn whether tumors in a mouse model of liver cancer had reduced levels of specific microRNAs and to determine the effects of restoring normal levels of these microRNAs to these cancer cells. We were very excited to see that the tumors were, in fact, very vulnerable to microRNA replacement”
Mendell and his team discovered that the tumor cells in the mouse were indeed sensitive to the restoration of the microRNA. “This concept of replacing microRNAs that are expressed in high levels in normal tissues but lost in diseases hasn’t been explored before,” Mendell says.
The Hopkins team showed that in a Petri dish, replacing microRNAs in lymphoma cells stopped the formation of tumors, Mendell stating that “Our work raises the possibility of a more general therapeutic approach that is based on restoring microRNAs to diseased tissues.”
The scientist chose liver because of its large function in detoxification and because it is a relatively accessible target for the delivery of small molecules.
They injected a virus containing microRNA in a group of mice and a virus containing no microRNA in another group of mice.
Six of eight injected with the virus without microRNa experienced in three weeks time an aggressive disease progression. In contrast,
eight of ten mice treated with microRNA exhibited only small tumors or complete absence of tumors.
As a conclusion to this experiment, Mendell said “The livers of the mice that received the microRNA virus glowed fluorescent green, showing that the microRNA ended up where it was supposed to go, and the cancer was largely suppressed.”
He also reported that
“The tumor cells that received the microRNA were rapidly dying while the normal liver cells were completely spared. 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.”
The study concludes by saying that the sensitivity of tumor cells to this microRNA suggests that its absence is a cause in the transformation of normal cells in cancer cells and that this discovery will help the development of strategies to ease patients diagnosed with liver cancer.
National Institutes of Health, the Sol Goldman Center for Pancreatic Cancer Research and the Research Institute at Nationwide Children’s Hospital supported the research.
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