Discovery method for reactivating cancer genes "silenced" by cancer

UCL scientists have developed a method to reactivate the "tumor suppressor" genes, which are deactivated by cancer cells – a discovery that could lead to new targeted biotherapies for cancer.

In the study, published in Nature Structural and Molecular BiologyResearchers at the UCL Cancer Institute and the UK Cancer Research Center for cancer research have looked for ways to block the functioning of a regulatory protein called PRC2 (Polycomb repressive complex 2).

Healthy cells use PRC2 to silence genes whose instructions should only be read by other types of cells. Cancer cells "hijack" this function of inhibiting PRC2 to disable the "tumor suppressor" genes. When they are active, these genes prevent cells from dividing. Therefore, if PRC2 could be removed from these genes, it could stop tumor growth.

Using healthy cells grown in the laboratory, researchers discovered that PRC2 also binds to RNA, the information molecule produced by active genes. When PRC2 binds to RNA, it can no longer bind or silence the gene.

Using cancer cells in the laboratory, researchers used a protein called dCas9 (Cas9 endonuclease death) to bind RNA to silenced tumor suppressor genes. RNA specifically removed PRC2 from the tumor suppressor gene to which it was attached, reactivating the gene and preventing the cancer cells from dividing.

Lead author, Professor Richard Jenner (UCL Cancer Institute), said: "Our discovery provides a way to accurately reverse the mutating events of cancerous genes, while leaving the other deactivated genes such as they are supposed to be.

"The next steps are to test the types of cancer to which this could be applied and to develop a method that could be used to deliver the targeting agent for RNA and gene to cancer cells in patients."