Scientists in Beersheba have found that a type of brain cancer called glioblastoma and aging of the brain in people who do not suffer from that malignancy have something in common – a specific gene.
Dr. Barak Rotblat of Beersheba’s Ben-Gurion University (BGU) of the Negev and colleagues in the life sciences department of the Faculty of Natural Sciences and the National Institute for Biotechnology in the Negev (NIBN) have just published their findings in the journal Aging. It appeared in the peer-reviewed journal under the title “TP73-AS1 is induced by YY1 during TMZ treatment and highly expressed in the aging brain.”
His team members included Gal Mazor, Dmitri Smirnov, Hila Ben David, and Dr. Debra Toiber of BGU’s life sciences department and Ekaterina Khrameeva of the Center of Life Sciences, Skolkovo Institute of Science and Technology, a private research institute in Moscow.
Glioblastoma multiform (GBM) is a brain cancer with a dismal outcome and a five-year survival rate of only up to 10%. Its location in the brain, recurrence and tendency to enter areas adjacent to the primary tumor are some of the major features contributing to its aggressiveness. Current treatments rely on surgery, radiotherapy and giving the drug temozolomide, which extends patient survival somewhat, but the tumor cells’ resistance to therapy is a major limiting factor in extending life of the patient. So, the researchers wrote, “it is important to advance our understanding of resistance mechanisms for the development of new, much-needed therapies.”
The gene that is activated in glioblastoma is partly responsible for aging in our brain. Studying cancer teaches us about aging and vis versa,” declared Rotblat. The team’s research focused on a new class of genes coding for long noncoding RNA. Classically, gene products are RNA that code for proteins. “But 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,” he said.
“For the past few years, we have been studying one of these genes, named 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,” Rotblat continued. 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 unknown.
“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,” Rotblat said. A
NIBN is a unique bio-accelerator located on the BGU – the first self-organized, independent research entity established under the auspices of an Israeli university. It works at accelerating BGU’s bio-applied translational discovery and research, through successful proof-of-concept and commercialization. Research at the NIBN is focused in several key areas including cancer, neurodegenerative diseases, autoimmune and metabolic diseases, applied biotechnology, infectious diseases, human genetic disorders and agbio (this industry is innovating to combat climate change and feed the globe with more sustainable solutions).