Blocking the METTL3 protein may enhance the effectiveness of chemotherapy in neuroblastoma, according to new findings. This research reveals how certain RNA modifications influence gene expression during the early stages of neuroblastoma development.
According to research from the University of Gothenburg, blocking the METTL3 protein could make neuroblastoma more responsive to chemotherapy. The study examines how specific RNA modifications impact gene expression in the early growth of neuroblastoma.
The experiments were carried out on mice, with the results published in The EMBO Journal. While the focus of this research is on understanding neuroblastoma mechanisms, it could serve as a foundation for further clinical research.
“The METTL3 protein might serve as a target for developing effective inhibitors that could reduce tumor growth and improve chemotherapy outcomes for neuroblastoma patients,” states Tanmoy Mondal, the lead researcher from the University of Gothenburg.
Neuroblastoma is a cancer originating in peripheral nerve tissues, mostly affecting young children. The disease can vary significantly in severity; while many cases may resolve on their own, some children face a form that is highly treatment-resistant and has a poor prognosis.
A promising new treatment
This study indicates that inhibiting METTL3 might offer a new treatment avenue for high-risk neuroblastoma, particularly in cases that do not respond to existing therapies.
Researchers discovered the METTL3 protein plays a crucial role in neuroblastoma by modifying gene expressions that regulate cell growth. By targeting METTL3, which controls m6A RNA modification, they were able to encourage cancer cells to differentiate, making them more susceptible to treatments. This differentiation caused the cancer cells to behave more like healthy cells.
When METTL3-inhibiting drugs were combined with chemotherapy, researchers noted a greater reduction in tumor size in the mice compared to those receiving chemotherapy alone.
Development of mature nerve cells
The study investigates how RNA modifications affect cancer cell conduct. It reveals that METTL3 alters HOX gene expressions, leading to a more aggressive and undifferentiated cancer state. HOX genes play a key role in transforming stem cells into mature nerve cells, and their expression is often disrupted in neuroblastoma.
“By inhibiting METTL3, we could reverse this process, allowing cancer cells to mature and shed their aggressive traits. This could be particularly beneficial for treating MYCN-amplified neuroblastoma, a type linked to poor outcomes,” remarks Ketan Thombare, a doctoral student at the University of Gothenburg and one of the primary authors.
Despite the encouraging findings, additional research is essential to explore how METTL3 inhibitors could be effectively applied in clinical scenarios.
“We are optimistic that our findings will lead to new clinical trials and ultimately result in treatments that can save lives,” adds Roshan Vaid, another lead author and postdoctoral research fellow at the University of Gothenburg.
The study involved collaboration with research teams from institutions in Sweden, as well as in Germany, the United Kingdom, and South Korea.
