Genome stability disrupted by the circRBM39(4,5,6)-RPA2 axis represses breast tumorigenesis.

CircRBM39(4,5,6) suppresses breast tumorigenesis by destabilizing RPA2 and enhancing DNA damage, with a 7-nt AG-rich motif critical for interaction.

• Why it matters: Understanding how circular RNAs regulate genome instability offers new avenues for cancer therapy, especially since GI is a hallmark of tumor progression and drug resistance.
• What they did: Researchers identified circRBM39(4,5,6) through profiling and siRNA screening, revealing its decreased levels in breast cancer and its role in promoting DNA damage and drug sensitivity.
• The result: Administering synthetic circRBM39(4,5,6) inhibits tumor growth, increases sensitivity to PARP inhibitors, and enables synthetic lethality, suggesting promising RNA-based therapeutic strategies.