Researchers at Karolinska Institutet in Sweden have identified a new so-called pseudogene that regulates the tumour-suppressing PTEN gene. They hope that this pseudogene will be able to control PTEN to reverse the tumour process, make the cancer tumour more sensitive to chemotherapy and to prevent the development of resistance. The findings, which are published in the scientific journal Nature Structural and Molecular Biology, can be of significance in the future development of cancer drugs.
The development of tumours coincides with the activation of several cancer genes as well as the inactivation of other tumour-suppressing genes owing to damage to the DNA and to the fact that the cancer cells manage to switch off the transcription of tumour-suppressor genes. To identify what might be regulating this silencing, the researchers studied PTEN, one of the most commonly inactivated tumour-suppressor genes. It has long been believed that the switching-off process is irreversible, but the team has now shown that silenced PTEN genes in tumour cells can be 'rescued' and re-activated by a 'pseudogene', a type of gene that, unlike normal genes, does not encode an entire protein.
"We identified a new non-protein encoding pseudogene, which determines whether the expression of PTEN is to be switched on or off," says research team member Per Johnsson, doctoral student at Karolinska Institutet's Department of Oncology-Pathology. "What makes this case spectacular is that the gene only produces RNA, the protein's template. It is this RNA that, through a sequence of mechanisms, regulates PTEN. Pseudogenes have been known about for many years, but it was thought that they were only junk material."
No less than 98 per cent of human DNA consists of non-protein encoding genes (i.e. pseudogenes), and by studying these formerly neglected genes the researchers have begun to understand that they are very important and can have an effect without encodin
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