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Interplay among mitochondria and p53 family proteins during apoptosis induced by dna damage - a new strategy for cancer therapy

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Target molecules identified by RNA interference

The unravelling of biochemical pathways may well hold the key to understanding cellular mechanisms in tumours. As part of this drive, a European project has investigated RNA interference as a basis for molecular target validation technology.

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The production of certain proteins as a result of gene expression in tumour cells can influence the development of a cancer. RNA interference (RNAi) is a means by which gene expression can be regulated, in some cases inhibited altogether. During this pathway, short RNA fragments known as small interfering RNA (siRNA) are produced. These are exactly complementary to the genes they are suppressing. Suppression, or the reduction of the levels of key proteins in the development of malignant cells is an exciting area in anticancer drug development. Apoptosis, or programmed cell death, is another pathway that can be utilised in the fight against malignant cells. Partners in the European funded project IMPALED researched these cell suicide cascades and their molecular constituents. In conjunction with this, scientists at Eirx Therapeutics in Ireland worked on a novel validation platform using siRNA. This aimed to study the consequences of knocking out molecular targets as identified by other project partners. The objective was to identify the proteins not produced as a result of the RNA interference technology. Knock-out rates for the proteins targeted by siRNA designed by Eirx were significantly high. The Western blotting technique was used to confirm the reduction of protein expression from these target genes. Furthermore, the team at Eirx also developed a speedy method to deliver siRNA into the cells with a resultant limited toxicity due to the fast transfection rate. The identification of these apoptotic molecular components can form the basis of the bid to determine the role of programmed cell death in cancer. It may also shed light on the reasons for resistance of cancerous cells to chemo- and radio-therapy treatment.

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