Researchers have identified a new molecular mechanism contributing to the development and progression of lung cancer. The study, conducted by investigators at GENyO, the University of Granada, and the Granada Institute for Health Research, focuses on the RBM10 gene and reveals how its alteration impacts RNA molecules that play a critical role in controlling tumor growth.
Lung cancer remains the leading cause of cancer-related deaths worldwide, according to the research.
Lung cancer continues to be the primary cause of cancer mortality globally. Approximately 2.5 million new cases are diagnosed annually, resulting in over 1.8 million deaths – representing nearly 18% of all cancer-related fatalities, according to recent estimates from the World Health Organization and the GLOBOCAN project. In Spain, it remains the deadliest form of cancer, and is projected to cause around 22,000 deaths in 2025 alone, data from the Spanish Society of Medical Oncology (SEOM) indicates. Despite advances in treatment, approximately 80% of lung cancer patients do not survive beyond five years after diagnosis, highlighting the urgent need for continued research.
When RBM10 doesn’t function properly, that control is lost and the tumor could grow more easily.
In the most common type of lung cancer, adenocarcinoma, RBM10 is frequently found to be altered. The gene functions as an internal regulator within cells, influencing how genetic instructions are utilized. When RBM10 isn’t working correctly, this control is compromised, potentially allowing tumors to grow more rapidly.
The research demonstrates that RBM10 influences the production of circular RNAs – molecules that don’t produce proteins but help maintain cellular balance. When RBM10 functions properly, it promotes the presence of specific circular RNAs that help suppress tumor growth. Conversely, when RBM10 is altered, these RNAs decrease, potentially enabling the tumor to advance more easily.
“We’ve observed that RBM10 acts as a kind of regulator,” explains Ana Utrilla, a lead author of the study, alongside Ana Matía and Paola Peinado. “When this gene fails, the balance of these circular RNAs is disrupted, and the cell loses some of its control mechanisms against cancer.”
One of these circular RNAs, called circHIPK3, was consistently found to be reduced in samples from patients with lung cancer, particularly those with mutations in RBM10. Researchers found that restoring levels of this circular RNA in tumor cells and animal models significantly reduced tumor growth.
In addition to helping to better understand the mechanisms involved in tumor development, these results could have potential clinical applications in the future.
Beyond enhancing our understanding of tumor development, these findings may have future clinical implications. The reduction of circHIPK3 could potentially serve as a biomarker to identify specific tumor states. The study also suggests that restoring the balance of these circular RNAs could turn into a complementary strategy for certain patients; however, these are preclinical findings and further research is needed to confirm their safety and efficacy. “This study opens a new avenue for developing more accurate diagnostic tools and, in the long term, new treatment options for patients whose tumors have lost this control mechanism,” says Pedro Pablo Medina Vico, Professor at the University of Granada and director of the perform.
This work was funded by research projects from the Regional Government of Andalusia and the Spanish Government, as well as private donations from Rosario Martín, of Écija, the ROLUCAN Association (Rota Fight Against Cancer), and the Spanish Association Against Cancer.
