BACKGROUND: Circular RNAs (circRNAs) are RNA transcripts that are widespread in 
the eukaryotic genome. Recent evidence indicates that circRNAs play important 
roles in tissue development, gene regulation, and carcinogenesis. However, 
whether circRNAs encode functional proteins remains elusive, although 
translation of several circRNAs was recently reported.
METHODS: CircRNA deep sequencing was performed by using 10 pathologically 
diagnosed glioblastoma samples and their paired adjacent normal brain tissues. 
Northern blotting, Sanger sequencing, antibody, and liquid chromatograph Tandem 
Mass Spectrometer were used to confirm the existence of circ-FBXW7 and its 
encoded protein in in two cell lines. Lentivirus-transfected stable U251 and 
U373 cells were used to assess the biological functions of the novel protein 
invitro and invivo (five mice per group). Clinical implications of circ-FBXW7 
were assessed in 38 pathologically diagnosed glioblastoma samples and their 
paired periphery normal brain tissues by using quantitative polymerase chain 
reaction (two-sided log-rank test).
RESULTS: Circ-FBXW7 is abundantly expressed in the normal human brain (reads per 
kilobase per million mapped reads [RPKM] = 9.31). The spanning junction open 
reading frame in circ-FBXW7 driven by internal ribosome entry site encodes a 
novel 21-kDa protein, which we termed FBXW7-185aa. Upregulation of FBXW7-185aa 
in cancer cells inhibited proliferation and cell cycle acceleration, while 
knockdown of FBXW7-185aa promoted malignant phenotypes invitro and invivo. 
FBXW7-185aa reduced the half-life of c-Myc by antagonizing USP28-induced c-Myc 
stabilization. Moreover, circ-FBXW7 and FBXW7-185aa levels were reduced in 
glioblastoma clinical samples compared with their paired tumor-adjacent tissues 
(P < .001). Circ-FBXW7 expression positively associated with glioblastoma 
patient overall survival (P = .03).
CONCLUSIONS: Endogenous circRNA encodes a functional protein in human cells, and 
circ-FBXW7 and FBXW7-185aa have potential prognostic implications in brain 
cancer.