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Scientists find surprising new influence on cancer genes

of their presumed inactivity. Pseudogenes, which make up vast swaths of non-coding DNA, were considered part of the junkeven though they resembled genesbecause they did not code for proteins.

The results from the new study contradict that view by showing these bits of genetic material playing a profound role in controlling the activity of human genes. The control or loss of control of genes can make the difference between healthy and diseased tissue. In cancer, for instance, some genes become more active, while other genes that should normally shut down a cancerous growth become suppressed.

In the new work, Morris and his colleagues showed that pseudogenes can influence the activity of a human gene known as the phosphatase and tensin homolog (PTEN). PTEN has long been implicated in cancer and is categorized as a "tumor suppressor" gene, meaning that it has the ability to arrest the growth of a tumor. But in many forms of cancer, PTEN is shut down, allowing the tumor to grow unchecked.

Intriguing Possibilities

Morris and his colleagues found that pseudogenes sharing sequences in common with PTEN can regulate the gene in two waysknocking it down by suppressing the "promoter" for the PTEN gene, preventing the gene from being expressed, or soaking up PTEN-targeted regulatory micro-RNAs affecting the PTEN protein after the gene transcripts have been expressed.

Some companies are already looking at pseudogenes such as PTEN as targets of potential new drugs, Morris said, and the new work is a proof of principle that targeting pseudogenes can modulate the growth of cancer cells grown in the laboratory.

The same principle may be applicable to other diseases where the aberrant activity of a normal human gene is in playor in infectious diseases, as a way of shutting down certain crucial genes belonging to viruses or bacteria.

Morris noted, however, there are many practical issues with controlling pseudoge

Contact: Mika Ono
Scripps Research Institute

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