Genetic link between aging brain and brain cancers discovered by Israeli scientists

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Using computer and cell biology techniques, such as CRISPR scientists have identified a protein that increases the activity of the TP73-AS1 gene in response to chemotherapy and is also known to activate many genes in the aging brain.

Scientists at the Israeli University – Ben Gurion University of the Negev (BGU) have discovered that a gene activated in glioblastoma, a type of brain cancer, is also partly responsible for the aging of our brains. Their findings were published in the peer-reviewed journal Aging at the end of last week.

“The study of cancer teaches us about aging and vice versa,” says lead researcher Dr Barak Rotblat of the Department of Life Sciences at the Faculty of Natural Sciences and the Negev National Institute of Biotechnology (NIBN ). Rotblat’s research focused on a new class of genes encoding non-coding long RNA. Conventionally, gene products are RNAs which code for proteins. However, while there are 20,000 genes encoding “classic” proteins, scientists now know that there are at least 20,000 genes whose products are long non-coding RNAs.

“In recent years, we have studied one of these genes, TP73-AS1, and found that it is very active in pediatric (medulloblastoma) and adult (glioblastoma) brain cancers. Importantly, not only is this gene very active in brain cancer, it also contributes to the aggressiveness of the disease. In glioblastoma, high levels of TP73-AS1 in tumor cells provide protection against chemotherapy, ”explains Dr Rotblat.

Using computer and cell biology techniques, such as CRISPR, the Rotblat laboratory identified a protein that increases the activity of the TP73-AS1 gene in response to chemotherapy and realized that this protein, known as named YY1, is also known to activate many genes in the aging brain. Interestingly, aging and glioblastoma are also known to be linked, as glioblastoma is more aggressive in older people. However, the genes linking the aging brain to glioblastoma were not known.

“Once we found out that YY1 increases the activity of TP73-AS1, we asked if, like YY1, TP73-AS1 is also active in the aging brain and found that it is. Now we are excited by the prospect that by studying TP73-AS1 and the molecular pathways with which it interacts, we can learn more about cancer and aging in the brain, ”says Dr. Rotblat of directions for future studies.

The research was supported by the Israel Science Foundation, the Israel Cancer Association, NIBN, the David and Inez Myers Foundation, and the Ministry of Science and Technology.


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