This study investigates the novel role of circular RNA (circRNA) FBXW7 in repressing glioma tumorigenesis. CircRNA deep sequencing was performed on 10 pathologically diagnosed glioblastoma samples and their paired adjacent normal brain tissues. The results identified circ-FBXW7, which encodes a novel 21-kDa protein termed FBXW7-185aa. FBXW7-185aa was found to inhibit cell proliferation and cell cycle acceleration in vitro and in vivo, while its knockdown promoted malignant phenotypes. FBXW7-185aa reduced the half-life of c-Myc by antagonizing USP28-induced c-Myc stabilization. Clinical samples showed that circ-FBXW7 and FBXW7-185aa levels were reduced in glioblastoma compared to adjacent normal tissues, and higher expression of circ-FBXW7 was associated with better overall survival in glioblastoma patients. These findings suggest that circ-FBXW7 and FBXW7-185aa have potential prognostic implications in brain cancer and may serve as tumor suppressors.This study investigates the novel role of circular RNA (circRNA) FBXW7 in repressing glioma tumorigenesis. CircRNA deep sequencing was performed on 10 pathologically diagnosed glioblastoma samples and their paired adjacent normal brain tissues. The results identified circ-FBXW7, which encodes a novel 21-kDa protein termed FBXW7-185aa. FBXW7-185aa was found to inhibit cell proliferation and cell cycle acceleration in vitro and in vivo, while its knockdown promoted malignant phenotypes. FBXW7-185aa reduced the half-life of c-Myc by antagonizing USP28-induced c-Myc stabilization. Clinical samples showed that circ-FBXW7 and FBXW7-185aa levels were reduced in glioblastoma compared to adjacent normal tissues, and higher expression of circ-FBXW7 was associated with better overall survival in glioblastoma patients. These findings suggest that circ-FBXW7 and FBXW7-185aa have potential prognostic implications in brain cancer and may serve as tumor suppressors.