Israeli university- Ben-Gurion University of Negev (BGU) scientists have found that a gene activated in glioblastoma, a type of brain cancer, is also partly responsible for aging in our brain.
Their findings were published in the peer-reviewed journal Aging late last week.
“Studying cancer teaches us about aging and vice versa,” says lead researcher Dr. Barak Rotblat of the Department of Life Sciences in the Faculty of Natural Sciences and the National Institute for Biotechnology in the Negev (NIBN). Rotblat’s research has focused on a new class of genes coding for long noncoding RNA. Classically, gene products are RNA which code for proteins. However, while there are 20,000 “classic” protein coding genes, we now know that there are at least 20,000 genes whose products are long noncoding RNA.
“For the past few years, we have been studying one of these genes, TP73-AS1, and found that it is highly active in both pediatric (medulloblastoma) and adult (glioblastoma) brain cancers. Importantly, not only is this gene highly active in brain cancer, but 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 computational and cell biology techniques, such as CRISPR, the Rotblat lab identified a protein increasing TP73-AS1 gene activity in response to chemotherapy and realized that this protein, known as YY1, is also known to activate many genes in the aging brain. Interestingly, aging and glioblastoma are also known to be linked, because glioblastoma is more aggressive in older people. However, the genes linking the aging brain to glioblastoma were not known.
“Once we found 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 this is indeed the case. Now, we are excited by the prospect that by studying TP73-AS1 and the molecular pathways it interacts with, we can learn about cancer and aging in the brain,” Dr Rotblat says about directions for future studies.
Additional researchers include Gal Mazor, Dmitri Smirnov, Hila Ben David, and Dr Debra Toiber of BGU’s Department of Life Sciences, and Ekaterina Khrameeva of the Center of Life Sciences, Skolkovo Institute of Science and Technology. Dr. Toiber is also a member of BGU’s Zlotowski Center for Neuroscience.
The research was supported by the Israel Science Foundation (grant No. 1436/19), by the Israeli Cancer Association (grant #20180012), the NIBN, The David and Inez Myers foundation and by the Ministry of Science and Technology.