New research published in Neuro-Oncology reveals findings that could influence future glioblastoma treatments and patient outcomes, according to a Jul. 29 announcement. A team of scientists from Virginia Commonwealth University, VCU Massey Comprehensive Cancer Center, and the University of Texas MD Cancer Center identified a protein called TRNAU1AP as playing an essential role in the survival and multiplication of glioblastoma cells.
By analyzing GBM tumor samples and public datasets, the researchers found that TRNAU1AP supports cancer stem cell survival and proliferation. Patients with higher levels of this protein were observed to have worse survival outcomes. The study showed that TRNAU1AP forms small clusters inside cells which help produce selective selenoproteins—proteins using selenium to protect cells from damage.
The research also highlighted another protein, IGF2BP3, which helps maintain high levels of TRNAU1AP in GBM tumor cells. This suggests that targeting the IGF2BP3-TRNAU1AP pathway could make glioblastoma cells more vulnerable to existing treatments. IGF2BP3 is described as an m6A reader protein; it recognizes a reversible chemical modification known as "m6A" on mRNA molecules and protects these modified RNAs from degradation. In GBM tumors, IGF2BP3 binds to m6A-modified TRNAU1AP mRNA, increasing its stability and supporting continued production of the TRNAU1AP protein necessary for tumor growth.
Looking ahead, Huang said he is interested in developing inhibitors targeting IGF2BP3 that can penetrate the blood-brain barrier as a potential therapy for glioblastoma patients. "A small-molecule inhibitor capable of entering the brain and disrupting IGF2BP3–RNA interactions could reduce the stability of these tumor-promoting transcripts and suppress glioblastoma growth," said Huang.
