RAPGEF4 can affect the sensitivity of lung cancer cells to cisplatin by altering cAMP levels through the Epac2-Rap1A-Akt pathway50 and is relevant to the pathogenesis of glioma.51 Although RAPGEF4 is not the only target of NOP2, our experiments demonstrated that RAPGEF4 is one of the downstream genes regulated by NOP2. Here, AKT1 is linked to central nervous system cancer.